/ en /news/scaling-up-spatial-genomics <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" class="datetime">April 3, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>A new computational approach eliminates time-intensive imaging, enabling high-resolution spatial mapping of gene expression in tissue.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" title="Thursday, April 3, 2025 - 05:00" class="datetime">April 3, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ffbkX92m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=8iiQYmFY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ChoROTIl 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc" alt="A spatial map of mouse embryo tissue with different colored dots representing cells." title="A spatial map of mouse embryo tissue with different colored dots representing cells." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Chenlei Hu, Chen lab </div> <div class="media-caption__description"> Spatial map of cell types in a mouse embryo. Each colored dot represents a different cell type. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/rss/news-blog-feed&amp;title=RSS%20Feed%20News%20%2B%20Blog" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> 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class="node__content"> <a href="/news/chemical-approach-imaging-cells-inside" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">A chemical approach to imaging cells from the inside</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Spatial transcriptomics technologies opened the door for new kinds of biological measurements, allowing scientists to generate detailed maps of where genes are expressed in tissue. But most methods rely on expensive and time-intensive imaging that requires specialized equipment.</p> <p>A new method developed by researchers at the ӳ����ý promises to make spatial transcriptomics easier for scientists to use. The approach eliminates the need for imaging and instead uses computational methods to reconstruct the spatial locations of gene expression. The team showed that by using their method, they could map larger sections of tissue more quickly and cheaply than with previous methods. They add that, more importantly, the new approach requires no specialized equipment and can be used by more researchers around the world. The work appears today in <em><a href="https://www.nature.com/articles/s41587-025-02612-0" target="_blank">Nature Biotechnology</a></em>.</p> <p>“Our work converts imaging into molecular biology — just a reaction in a test tube,” said <a href="/node/113836">Fei Chen</a>, who is a senior author on the study, a core institute member at the ӳ����ý, and an assistant professor in the Department of Stem Cell and Regenerative Biology at Harvard University. “That means anybody can use this approach if they have the algorithm and some common materials.”</p> <p>“When biologists think about spatial locations, they might think they need to look at samples with light microscopy or electron microscopy,” added Chenlei Hu. Hu is the first author on the work and a Harvard graduate student in Chen’s lab. “But we’ve found that we can computationally infer physical locations instead.”</p> <h2>Mapping with beads</h2> <p>The new findings build on a technique called <a href="https://www.science.org/doi/10.1126/science.aaw1219" target="_blank">Slide-seq</a>, which was developed by Chen, ӳ����ý core institute member <a href="/node/652411">Evan Macosko</a>, and colleagues in 2019. The method generates high-resolution maps of gene expression across tissue. Researchers first collect images of an array of DNA-barcoded beads on a slide, creating a reference that tells the location of each bead. Next, they place a tissue section on the beads and dissolve it, leaving messenger RNA from the tissue bound to the barcoded beads. They then load the beads into a sequencer and use specialized software to create a map of gene expression across the tissue.</p> <p>In the past, Chen’s lab made the arrays and imaged them for other scientists. Their microscope was under near-constant use. But lingering in their minds was the possibility that they could infer the location of each bead with sequencing alone, eliminating the need for imaging.&nbsp;</p> <p>They thought that if you knew the distance between every pair of beads on the array, you could reconstruct their spatial positions — in the same way you can locate a cell phone by knowing its distance from satellites.</p> <p>When she joined Chen’s lab, Hu thought it might be possible to pinpoint the location of the beads by measuring how much molecules diffuse between them. She and her colleagues built a new kind of bead array containing both “transmitter” and “receiver” beads, each with DNA barcodes. When exposed to UV light, the barcodes cleave from the transmitter beads, diffuse away, and are captured by the receiver beads. Receiver beads that are closer to transmitters will capture more DNA barcodes as they diffuse from the transmitters. Slide-seq’s sequencing step can measure the level of these captured barcodes, providing information not only about gene expression, but also the location of the beads. Hu then used an algorithm commonly used in single-cell analysis called Uniform Manifold Approximation and Projection (UMAP) to reconstruct the beads’ original locations on the slide.</p> <p>When the researchers used their method and the image-based Slide-seq to analyze the same sample, they found very little difference. Without the time-intensive imaging step, Chen’s team was able to map gene expression across larger sections of tissue than before: areas up to 1.2 centimeters wide of mouse embryo tissue (previous maps covered only about 3 millimeters). The Chen group is now working with the Macosko lab to map areas as large as 7 centimeters, close to the size of entire organs in people.</p> <p>“We’re no longer limited by how long it takes us to image something," Chen said. “Eventually we’d like to analyze the whole human brain. That just wasn’t possible with other technologies.”<br> &nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health (NHGRI) and the Opportunity Fund through the Technology Development Coordinating Center at Jackson Laboratories.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Hu, C et al. <a href="https://www.nature.com/articles/s41587-025-02612-0">Scalable spatial transcriptomics through computational array reconstruction</a>. <em>Nature Biotechnology</em>. Online April 3, 2025. DOI: 10.1038/s41587-025-02612-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/spatial-omics-0" hreflang="en">Spatial -omics</a></div> <div class="field__item"><a href="/broad-tags/evan-macosko" hreflang="en">Evan Macosko</a></div> <div class="field__item"><a href="/broad-tags/fei-chen" hreflang="en">Fei Chen</a></div> </div> </div> </div> </div> </div> Thu, 03 Apr 2025 09:00:00 +0000 adicorat 5558321 at /news/building-bridges-between-denmark-based-and-broad-researchers <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" class="datetime">April 3, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>A new computational approach eliminates time-intensive imaging, enabling high-resolution spatial mapping of gene expression in tissue.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" title="Thursday, April 3, 2025 - 05:00" class="datetime">April 3, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ffbkX92m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=8iiQYmFY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ChoROTIl 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc" alt="A spatial map of mouse embryo tissue with different colored dots representing cells." title="A spatial map of mouse embryo tissue with different colored dots representing cells." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Chenlei Hu, Chen lab </div> <div class="media-caption__description"> Spatial map of cell types in a mouse embryo. Each colored dot represents a different cell type. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/rss/news-blog-feed&amp;title=RSS%20Feed%20News%20%2B%20Blog" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> 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media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/new-tool-uses-rna-sequencing-chart-rich-maps-cellular-and-tissue-function"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/Projections_of_Composite_MainStoryPage_1.gif?itok=mjfz_ovm 1x" media="all and (min-width: 1921px)" type="image/gif" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/Projections_of_Composite_MainStoryPage_1.gif?itok=mjfz_ovm 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/gif" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/Projections_of_Composite_MainStoryPage_1.gif?itok=6B1IxztQ 1x" media="all and (min-width: 1340px) and (max-width: 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of how slide-DNA-seq &quot;sees&quot; cells' organization within a tumor." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/new-dna-sequencing-technique-preserves-cells%E2%80%99-locations-within-tissues" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">New DNA sequencing technique preserves cells’ locations within tissues</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/chemical-approach-imaging-cells-inside" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/chemical-approach-imaging-cells-inside"><picture> <source 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srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/Micro_for%20web.jpg?h=58f9d142&amp;itok=OOV3PSI_ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/Micro_for%20web.jpg?h=58f9d142&amp;itok=qZS7f2n4 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/Micro_for%20web.jpg?h=58f9d142&amp;itok=qZS7f2n4" alt="A visualization of the data for a sample provided by DNA microscopy, with random colors assigned to individual inferred cells." title="A visualization of the data for a sample provided by DNA microscopy, with random colors assigned to individual inferred cells." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/chemical-approach-imaging-cells-inside" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">A chemical approach to imaging cells from the inside</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Spatial transcriptomics technologies opened the door for new kinds of biological measurements, allowing scientists to generate detailed maps of where genes are expressed in tissue. But most methods rely on expensive and time-intensive imaging that requires specialized equipment.</p> <p>A new method developed by researchers at the ӳ����ý promises to make spatial transcriptomics easier for scientists to use. The approach eliminates the need for imaging and instead uses computational methods to reconstruct the spatial locations of gene expression. The team showed that by using their method, they could map larger sections of tissue more quickly and cheaply than with previous methods. They add that, more importantly, the new approach requires no specialized equipment and can be used by more researchers around the world. The work appears today in <em><a href="https://www.nature.com/articles/s41587-025-02612-0" target="_blank">Nature Biotechnology</a></em>.</p> <p>“Our work converts imaging into molecular biology — just a reaction in a test tube,” said <a href="/node/113836">Fei Chen</a>, who is a senior author on the study, a core institute member at the ӳ����ý, and an assistant professor in the Department of Stem Cell and Regenerative Biology at Harvard University. “That means anybody can use this approach if they have the algorithm and some common materials.”</p> <p>“When biologists think about spatial locations, they might think they need to look at samples with light microscopy or electron microscopy,” added Chenlei Hu. Hu is the first author on the work and a Harvard graduate student in Chen’s lab. “But we’ve found that we can computationally infer physical locations instead.”</p> <h2>Mapping with beads</h2> <p>The new findings build on a technique called <a href="https://www.science.org/doi/10.1126/science.aaw1219" target="_blank">Slide-seq</a>, which was developed by Chen, ӳ����ý core institute member <a href="/node/652411">Evan Macosko</a>, and colleagues in 2019. The method generates high-resolution maps of gene expression across tissue. Researchers first collect images of an array of DNA-barcoded beads on a slide, creating a reference that tells the location of each bead. Next, they place a tissue section on the beads and dissolve it, leaving messenger RNA from the tissue bound to the barcoded beads. They then load the beads into a sequencer and use specialized software to create a map of gene expression across the tissue.</p> <p>In the past, Chen’s lab made the arrays and imaged them for other scientists. Their microscope was under near-constant use. But lingering in their minds was the possibility that they could infer the location of each bead with sequencing alone, eliminating the need for imaging.&nbsp;</p> <p>They thought that if you knew the distance between every pair of beads on the array, you could reconstruct their spatial positions — in the same way you can locate a cell phone by knowing its distance from satellites.</p> <p>When she joined Chen’s lab, Hu thought it might be possible to pinpoint the location of the beads by measuring how much molecules diffuse between them. She and her colleagues built a new kind of bead array containing both “transmitter” and “receiver” beads, each with DNA barcodes. When exposed to UV light, the barcodes cleave from the transmitter beads, diffuse away, and are captured by the receiver beads. Receiver beads that are closer to transmitters will capture more DNA barcodes as they diffuse from the transmitters. Slide-seq’s sequencing step can measure the level of these captured barcodes, providing information not only about gene expression, but also the location of the beads. Hu then used an algorithm commonly used in single-cell analysis called Uniform Manifold Approximation and Projection (UMAP) to reconstruct the beads’ original locations on the slide.</p> <p>When the researchers used their method and the image-based Slide-seq to analyze the same sample, they found very little difference. Without the time-intensive imaging step, Chen’s team was able to map gene expression across larger sections of tissue than before: areas up to 1.2 centimeters wide of mouse embryo tissue (previous maps covered only about 3 millimeters). The Chen group is now working with the Macosko lab to map areas as large as 7 centimeters, close to the size of entire organs in people.</p> <p>“We’re no longer limited by how long it takes us to image something," Chen said. “Eventually we’d like to analyze the whole human brain. That just wasn’t possible with other technologies.”<br> &nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health (NHGRI) and the Opportunity Fund through the Technology Development Coordinating Center at Jackson Laboratories.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Hu, C et al. <a href="https://www.nature.com/articles/s41587-025-02612-0">Scalable spatial transcriptomics through computational array reconstruction</a>. <em>Nature Biotechnology</em>. Online April 3, 2025. DOI: 10.1038/s41587-025-02612-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/spatial-omics-0" hreflang="en">Spatial -omics</a></div> <div class="field__item"><a href="/broad-tags/evan-macosko" hreflang="en">Evan Macosko</a></div> <div class="field__item"><a href="/broad-tags/fei-chen" hreflang="en">Fei Chen</a></div> </div> </div> </div> </div> </div> Thu, 27 Mar 2025 17:19:09 +0000 Corie Lok 5558401 at /news/effort-based-broad-fostering-dialogue-between-autism-researchers-advocates-and-families <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" class="datetime">April 3, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>A new computational approach eliminates time-intensive imaging, enabling high-resolution spatial mapping of gene expression in tissue.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" title="Thursday, April 3, 2025 - 05:00" class="datetime">April 3, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ffbkX92m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=8iiQYmFY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ChoROTIl 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc" alt="A spatial map of mouse embryo tissue with different colored dots representing cells." title="A spatial map of mouse embryo tissue with different colored dots representing cells." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Chenlei Hu, Chen lab </div> <div class="media-caption__description"> Spatial map of cell types in a mouse embryo. Each colored dot represents a different cell type. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/rss/news-blog-feed&amp;title=RSS%20Feed%20News%20%2B%20Blog" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> 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field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/new-tool-uses-rna-sequencing-chart-rich-maps-cellular-and-tissue-function" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media 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class="node__content"> <a href="/news/chemical-approach-imaging-cells-inside" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">A chemical approach to imaging cells from the inside</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Spatial transcriptomics technologies opened the door for new kinds of biological measurements, allowing scientists to generate detailed maps of where genes are expressed in tissue. But most methods rely on expensive and time-intensive imaging that requires specialized equipment.</p> <p>A new method developed by researchers at the ӳ����ý promises to make spatial transcriptomics easier for scientists to use. The approach eliminates the need for imaging and instead uses computational methods to reconstruct the spatial locations of gene expression. The team showed that by using their method, they could map larger sections of tissue more quickly and cheaply than with previous methods. They add that, more importantly, the new approach requires no specialized equipment and can be used by more researchers around the world. The work appears today in <em><a href="https://www.nature.com/articles/s41587-025-02612-0" target="_blank">Nature Biotechnology</a></em>.</p> <p>“Our work converts imaging into molecular biology — just a reaction in a test tube,” said <a href="/node/113836">Fei Chen</a>, who is a senior author on the study, a core institute member at the ӳ����ý, and an assistant professor in the Department of Stem Cell and Regenerative Biology at Harvard University. “That means anybody can use this approach if they have the algorithm and some common materials.”</p> <p>“When biologists think about spatial locations, they might think they need to look at samples with light microscopy or electron microscopy,” added Chenlei Hu. Hu is the first author on the work and a Harvard graduate student in Chen’s lab. “But we’ve found that we can computationally infer physical locations instead.”</p> <h2>Mapping with beads</h2> <p>The new findings build on a technique called <a href="https://www.science.org/doi/10.1126/science.aaw1219" target="_blank">Slide-seq</a>, which was developed by Chen, ӳ����ý core institute member <a href="/node/652411">Evan Macosko</a>, and colleagues in 2019. The method generates high-resolution maps of gene expression across tissue. Researchers first collect images of an array of DNA-barcoded beads on a slide, creating a reference that tells the location of each bead. Next, they place a tissue section on the beads and dissolve it, leaving messenger RNA from the tissue bound to the barcoded beads. They then load the beads into a sequencer and use specialized software to create a map of gene expression across the tissue.</p> <p>In the past, Chen’s lab made the arrays and imaged them for other scientists. Their microscope was under near-constant use. But lingering in their minds was the possibility that they could infer the location of each bead with sequencing alone, eliminating the need for imaging.&nbsp;</p> <p>They thought that if you knew the distance between every pair of beads on the array, you could reconstruct their spatial positions — in the same way you can locate a cell phone by knowing its distance from satellites.</p> <p>When she joined Chen’s lab, Hu thought it might be possible to pinpoint the location of the beads by measuring how much molecules diffuse between them. She and her colleagues built a new kind of bead array containing both “transmitter” and “receiver” beads, each with DNA barcodes. When exposed to UV light, the barcodes cleave from the transmitter beads, diffuse away, and are captured by the receiver beads. Receiver beads that are closer to transmitters will capture more DNA barcodes as they diffuse from the transmitters. Slide-seq’s sequencing step can measure the level of these captured barcodes, providing information not only about gene expression, but also the location of the beads. Hu then used an algorithm commonly used in single-cell analysis called Uniform Manifold Approximation and Projection (UMAP) to reconstruct the beads’ original locations on the slide.</p> <p>When the researchers used their method and the image-based Slide-seq to analyze the same sample, they found very little difference. Without the time-intensive imaging step, Chen’s team was able to map gene expression across larger sections of tissue than before: areas up to 1.2 centimeters wide of mouse embryo tissue (previous maps covered only about 3 millimeters). The Chen group is now working with the Macosko lab to map areas as large as 7 centimeters, close to the size of entire organs in people.</p> <p>“We’re no longer limited by how long it takes us to image something," Chen said. “Eventually we’d like to analyze the whole human brain. That just wasn’t possible with other technologies.”<br> &nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health (NHGRI) and the Opportunity Fund through the Technology Development Coordinating Center at Jackson Laboratories.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Hu, C et al. <a href="https://www.nature.com/articles/s41587-025-02612-0">Scalable spatial transcriptomics through computational array reconstruction</a>. <em>Nature Biotechnology</em>. Online April 3, 2025. DOI: 10.1038/s41587-025-02612-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/spatial-omics-0" hreflang="en">Spatial -omics</a></div> <div class="field__item"><a href="/broad-tags/evan-macosko" hreflang="en">Evan Macosko</a></div> <div class="field__item"><a href="/broad-tags/fei-chen" hreflang="en">Fei Chen</a></div> </div> </div> </div> </div> </div> Tue, 25 Mar 2025 14:44:53 +0000 leah@broadinstitute.org 5558391 at /news/new-technology-puts-spatial-lens-crispr-screening <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" class="datetime">April 3, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>A new computational approach eliminates time-intensive imaging, enabling high-resolution spatial mapping of gene expression in tissue.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" title="Thursday, April 3, 2025 - 05:00" class="datetime">April 3, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ffbkX92m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=8iiQYmFY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ChoROTIl 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc" alt="A spatial map of mouse embryo tissue with different colored dots representing cells." title="A spatial map of mouse embryo tissue with different colored dots representing cells." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Chenlei Hu, Chen lab </div> <div class="media-caption__description"> Spatial map of cell types in a mouse embryo. Each colored dot represents a different cell type. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/rss/news-blog-feed&amp;title=RSS%20Feed%20News%20%2B%20Blog" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> 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of how slide-DNA-seq &quot;sees&quot; cells' organization within a tumor." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/new-dna-sequencing-technique-preserves-cells%E2%80%99-locations-within-tissues" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">New DNA sequencing technique preserves cells’ locations within tissues</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/chemical-approach-imaging-cells-inside" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/chemical-approach-imaging-cells-inside"><picture> <source 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class="node__content"> <a href="/news/chemical-approach-imaging-cells-inside" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">A chemical approach to imaging cells from the inside</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Spatial transcriptomics technologies opened the door for new kinds of biological measurements, allowing scientists to generate detailed maps of where genes are expressed in tissue. But most methods rely on expensive and time-intensive imaging that requires specialized equipment.</p> <p>A new method developed by researchers at the ӳ����ý promises to make spatial transcriptomics easier for scientists to use. The approach eliminates the need for imaging and instead uses computational methods to reconstruct the spatial locations of gene expression. The team showed that by using their method, they could map larger sections of tissue more quickly and cheaply than with previous methods. They add that, more importantly, the new approach requires no specialized equipment and can be used by more researchers around the world. The work appears today in <em><a href="https://www.nature.com/articles/s41587-025-02612-0" target="_blank">Nature Biotechnology</a></em>.</p> <p>“Our work converts imaging into molecular biology — just a reaction in a test tube,” said <a href="/node/113836">Fei Chen</a>, who is a senior author on the study, a core institute member at the ӳ����ý, and an assistant professor in the Department of Stem Cell and Regenerative Biology at Harvard University. “That means anybody can use this approach if they have the algorithm and some common materials.”</p> <p>“When biologists think about spatial locations, they might think they need to look at samples with light microscopy or electron microscopy,” added Chenlei Hu. Hu is the first author on the work and a Harvard graduate student in Chen’s lab. “But we’ve found that we can computationally infer physical locations instead.”</p> <h2>Mapping with beads</h2> <p>The new findings build on a technique called <a href="https://www.science.org/doi/10.1126/science.aaw1219" target="_blank">Slide-seq</a>, which was developed by Chen, ӳ����ý core institute member <a href="/node/652411">Evan Macosko</a>, and colleagues in 2019. The method generates high-resolution maps of gene expression across tissue. Researchers first collect images of an array of DNA-barcoded beads on a slide, creating a reference that tells the location of each bead. Next, they place a tissue section on the beads and dissolve it, leaving messenger RNA from the tissue bound to the barcoded beads. They then load the beads into a sequencer and use specialized software to create a map of gene expression across the tissue.</p> <p>In the past, Chen’s lab made the arrays and imaged them for other scientists. Their microscope was under near-constant use. But lingering in their minds was the possibility that they could infer the location of each bead with sequencing alone, eliminating the need for imaging.&nbsp;</p> <p>They thought that if you knew the distance between every pair of beads on the array, you could reconstruct their spatial positions — in the same way you can locate a cell phone by knowing its distance from satellites.</p> <p>When she joined Chen’s lab, Hu thought it might be possible to pinpoint the location of the beads by measuring how much molecules diffuse between them. She and her colleagues built a new kind of bead array containing both “transmitter” and “receiver” beads, each with DNA barcodes. When exposed to UV light, the barcodes cleave from the transmitter beads, diffuse away, and are captured by the receiver beads. Receiver beads that are closer to transmitters will capture more DNA barcodes as they diffuse from the transmitters. Slide-seq’s sequencing step can measure the level of these captured barcodes, providing information not only about gene expression, but also the location of the beads. Hu then used an algorithm commonly used in single-cell analysis called Uniform Manifold Approximation and Projection (UMAP) to reconstruct the beads’ original locations on the slide.</p> <p>When the researchers used their method and the image-based Slide-seq to analyze the same sample, they found very little difference. Without the time-intensive imaging step, Chen’s team was able to map gene expression across larger sections of tissue than before: areas up to 1.2 centimeters wide of mouse embryo tissue (previous maps covered only about 3 millimeters). The Chen group is now working with the Macosko lab to map areas as large as 7 centimeters, close to the size of entire organs in people.</p> <p>“We’re no longer limited by how long it takes us to image something," Chen said. “Eventually we’d like to analyze the whole human brain. That just wasn’t possible with other technologies.”<br> &nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health (NHGRI) and the Opportunity Fund through the Technology Development Coordinating Center at Jackson Laboratories.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Hu, C et al. <a href="https://www.nature.com/articles/s41587-025-02612-0">Scalable spatial transcriptomics through computational array reconstruction</a>. <em>Nature Biotechnology</em>. Online April 3, 2025. DOI: 10.1038/s41587-025-02612-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/spatial-omics-0" hreflang="en">Spatial -omics</a></div> <div class="field__item"><a href="/broad-tags/evan-macosko" hreflang="en">Evan Macosko</a></div> <div class="field__item"><a href="/broad-tags/fei-chen" hreflang="en">Fei Chen</a></div> </div> </div> </div> </div> </div> Wed, 12 Mar 2025 14:19:39 +0000 leah@broadinstitute.org 5558361 at /news/count-me-launches-new-patient-partnered-research-project-translocation-renal-cell-carcinoma <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" class="datetime">April 3, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>A new computational approach eliminates time-intensive imaging, enabling high-resolution spatial mapping of gene expression in tissue.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" title="Thursday, April 3, 2025 - 05:00" class="datetime">April 3, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ffbkX92m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=8iiQYmFY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ChoROTIl 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc" alt="A spatial map of mouse embryo tissue with different colored dots representing cells." title="A spatial map of mouse embryo tissue with different colored dots representing cells." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Chenlei Hu, Chen lab </div> <div class="media-caption__description"> Spatial map of cell types in a mouse embryo. Each colored dot represents a different cell type. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/rss/news-blog-feed&amp;title=RSS%20Feed%20News%20%2B%20Blog" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> 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of how slide-DNA-seq &quot;sees&quot; cells' organization within a tumor." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/new-dna-sequencing-technique-preserves-cells%E2%80%99-locations-within-tissues" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">New DNA sequencing technique preserves cells’ locations within tissues</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/chemical-approach-imaging-cells-inside" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/chemical-approach-imaging-cells-inside"><picture> <source 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class="node__content"> <a href="/news/chemical-approach-imaging-cells-inside" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">A chemical approach to imaging cells from the inside</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Spatial transcriptomics technologies opened the door for new kinds of biological measurements, allowing scientists to generate detailed maps of where genes are expressed in tissue. But most methods rely on expensive and time-intensive imaging that requires specialized equipment.</p> <p>A new method developed by researchers at the ӳ����ý promises to make spatial transcriptomics easier for scientists to use. The approach eliminates the need for imaging and instead uses computational methods to reconstruct the spatial locations of gene expression. The team showed that by using their method, they could map larger sections of tissue more quickly and cheaply than with previous methods. They add that, more importantly, the new approach requires no specialized equipment and can be used by more researchers around the world. The work appears today in <em><a href="https://www.nature.com/articles/s41587-025-02612-0" target="_blank">Nature Biotechnology</a></em>.</p> <p>“Our work converts imaging into molecular biology — just a reaction in a test tube,” said <a href="/node/113836">Fei Chen</a>, who is a senior author on the study, a core institute member at the ӳ����ý, and an assistant professor in the Department of Stem Cell and Regenerative Biology at Harvard University. “That means anybody can use this approach if they have the algorithm and some common materials.”</p> <p>“When biologists think about spatial locations, they might think they need to look at samples with light microscopy or electron microscopy,” added Chenlei Hu. Hu is the first author on the work and a Harvard graduate student in Chen’s lab. “But we’ve found that we can computationally infer physical locations instead.”</p> <h2>Mapping with beads</h2> <p>The new findings build on a technique called <a href="https://www.science.org/doi/10.1126/science.aaw1219" target="_blank">Slide-seq</a>, which was developed by Chen, ӳ����ý core institute member <a href="/node/652411">Evan Macosko</a>, and colleagues in 2019. The method generates high-resolution maps of gene expression across tissue. Researchers first collect images of an array of DNA-barcoded beads on a slide, creating a reference that tells the location of each bead. Next, they place a tissue section on the beads and dissolve it, leaving messenger RNA from the tissue bound to the barcoded beads. They then load the beads into a sequencer and use specialized software to create a map of gene expression across the tissue.</p> <p>In the past, Chen’s lab made the arrays and imaged them for other scientists. Their microscope was under near-constant use. But lingering in their minds was the possibility that they could infer the location of each bead with sequencing alone, eliminating the need for imaging.&nbsp;</p> <p>They thought that if you knew the distance between every pair of beads on the array, you could reconstruct their spatial positions — in the same way you can locate a cell phone by knowing its distance from satellites.</p> <p>When she joined Chen’s lab, Hu thought it might be possible to pinpoint the location of the beads by measuring how much molecules diffuse between them. She and her colleagues built a new kind of bead array containing both “transmitter” and “receiver” beads, each with DNA barcodes. When exposed to UV light, the barcodes cleave from the transmitter beads, diffuse away, and are captured by the receiver beads. Receiver beads that are closer to transmitters will capture more DNA barcodes as they diffuse from the transmitters. Slide-seq’s sequencing step can measure the level of these captured barcodes, providing information not only about gene expression, but also the location of the beads. Hu then used an algorithm commonly used in single-cell analysis called Uniform Manifold Approximation and Projection (UMAP) to reconstruct the beads’ original locations on the slide.</p> <p>When the researchers used their method and the image-based Slide-seq to analyze the same sample, they found very little difference. Without the time-intensive imaging step, Chen’s team was able to map gene expression across larger sections of tissue than before: areas up to 1.2 centimeters wide of mouse embryo tissue (previous maps covered only about 3 millimeters). The Chen group is now working with the Macosko lab to map areas as large as 7 centimeters, close to the size of entire organs in people.</p> <p>“We’re no longer limited by how long it takes us to image something," Chen said. “Eventually we’d like to analyze the whole human brain. That just wasn’t possible with other technologies.”<br> &nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health (NHGRI) and the Opportunity Fund through the Technology Development Coordinating Center at Jackson Laboratories.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Hu, C et al. <a href="https://www.nature.com/articles/s41587-025-02612-0">Scalable spatial transcriptomics through computational array reconstruction</a>. <em>Nature Biotechnology</em>. Online April 3, 2025. DOI: 10.1038/s41587-025-02612-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/spatial-omics-0" hreflang="en">Spatial -omics</a></div> <div class="field__item"><a href="/broad-tags/evan-macosko" hreflang="en">Evan Macosko</a></div> <div class="field__item"><a href="/broad-tags/fei-chen" hreflang="en">Fei Chen</a></div> </div> </div> </div> </div> </div> Tue, 11 Mar 2025 13:18:28 +0000 Corie Lok 5558201 at /news/studies-reveal-new-genetic-roots-atrial-fibrillation <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" class="datetime">April 3, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>A new computational approach eliminates time-intensive imaging, enabling high-resolution spatial mapping of gene expression in tissue.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" title="Thursday, April 3, 2025 - 05:00" class="datetime">April 3, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ffbkX92m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=8iiQYmFY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ChoROTIl 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc" alt="A spatial map of mouse embryo tissue with different colored dots representing cells." title="A spatial map of mouse embryo tissue with different colored dots representing cells." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Chenlei Hu, Chen lab </div> <div class="media-caption__description"> Spatial map of cell types in a mouse embryo. Each colored dot represents a different cell type. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/rss/news-blog-feed&amp;title=RSS%20Feed%20News%20%2B%20Blog" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> 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of how slide-DNA-seq &quot;sees&quot; cells' organization within a tumor." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/new-dna-sequencing-technique-preserves-cells%E2%80%99-locations-within-tissues" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">New DNA sequencing technique preserves cells’ locations within tissues</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/chemical-approach-imaging-cells-inside" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/chemical-approach-imaging-cells-inside"><picture> <source 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class="node__content"> <a href="/news/chemical-approach-imaging-cells-inside" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">A chemical approach to imaging cells from the inside</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Spatial transcriptomics technologies opened the door for new kinds of biological measurements, allowing scientists to generate detailed maps of where genes are expressed in tissue. But most methods rely on expensive and time-intensive imaging that requires specialized equipment.</p> <p>A new method developed by researchers at the ӳ����ý promises to make spatial transcriptomics easier for scientists to use. The approach eliminates the need for imaging and instead uses computational methods to reconstruct the spatial locations of gene expression. The team showed that by using their method, they could map larger sections of tissue more quickly and cheaply than with previous methods. They add that, more importantly, the new approach requires no specialized equipment and can be used by more researchers around the world. The work appears today in <em><a href="https://www.nature.com/articles/s41587-025-02612-0" target="_blank">Nature Biotechnology</a></em>.</p> <p>“Our work converts imaging into molecular biology — just a reaction in a test tube,” said <a href="/node/113836">Fei Chen</a>, who is a senior author on the study, a core institute member at the ӳ����ý, and an assistant professor in the Department of Stem Cell and Regenerative Biology at Harvard University. “That means anybody can use this approach if they have the algorithm and some common materials.”</p> <p>“When biologists think about spatial locations, they might think they need to look at samples with light microscopy or electron microscopy,” added Chenlei Hu. Hu is the first author on the work and a Harvard graduate student in Chen’s lab. “But we’ve found that we can computationally infer physical locations instead.”</p> <h2>Mapping with beads</h2> <p>The new findings build on a technique called <a href="https://www.science.org/doi/10.1126/science.aaw1219" target="_blank">Slide-seq</a>, which was developed by Chen, ӳ����ý core institute member <a href="/node/652411">Evan Macosko</a>, and colleagues in 2019. The method generates high-resolution maps of gene expression across tissue. Researchers first collect images of an array of DNA-barcoded beads on a slide, creating a reference that tells the location of each bead. Next, they place a tissue section on the beads and dissolve it, leaving messenger RNA from the tissue bound to the barcoded beads. They then load the beads into a sequencer and use specialized software to create a map of gene expression across the tissue.</p> <p>In the past, Chen’s lab made the arrays and imaged them for other scientists. Their microscope was under near-constant use. But lingering in their minds was the possibility that they could infer the location of each bead with sequencing alone, eliminating the need for imaging.&nbsp;</p> <p>They thought that if you knew the distance between every pair of beads on the array, you could reconstruct their spatial positions — in the same way you can locate a cell phone by knowing its distance from satellites.</p> <p>When she joined Chen’s lab, Hu thought it might be possible to pinpoint the location of the beads by measuring how much molecules diffuse between them. She and her colleagues built a new kind of bead array containing both “transmitter” and “receiver” beads, each with DNA barcodes. When exposed to UV light, the barcodes cleave from the transmitter beads, diffuse away, and are captured by the receiver beads. Receiver beads that are closer to transmitters will capture more DNA barcodes as they diffuse from the transmitters. Slide-seq’s sequencing step can measure the level of these captured barcodes, providing information not only about gene expression, but also the location of the beads. Hu then used an algorithm commonly used in single-cell analysis called Uniform Manifold Approximation and Projection (UMAP) to reconstruct the beads’ original locations on the slide.</p> <p>When the researchers used their method and the image-based Slide-seq to analyze the same sample, they found very little difference. Without the time-intensive imaging step, Chen’s team was able to map gene expression across larger sections of tissue than before: areas up to 1.2 centimeters wide of mouse embryo tissue (previous maps covered only about 3 millimeters). The Chen group is now working with the Macosko lab to map areas as large as 7 centimeters, close to the size of entire organs in people.</p> <p>“We’re no longer limited by how long it takes us to image something," Chen said. “Eventually we’d like to analyze the whole human brain. That just wasn’t possible with other technologies.”<br> &nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health (NHGRI) and the Opportunity Fund through the Technology Development Coordinating Center at Jackson Laboratories.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Hu, C et al. <a href="https://www.nature.com/articles/s41587-025-02612-0">Scalable spatial transcriptomics through computational array reconstruction</a>. <em>Nature Biotechnology</em>. Online April 3, 2025. DOI: 10.1038/s41587-025-02612-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/spatial-omics-0" hreflang="en">Spatial -omics</a></div> <div class="field__item"><a href="/broad-tags/evan-macosko" hreflang="en">Evan Macosko</a></div> <div class="field__item"><a href="/broad-tags/fei-chen" hreflang="en">Fei Chen</a></div> </div> </div> </div> </div> </div> Thu, 06 Mar 2025 10:00:00 +0000 leah@broadinstitute.org 5558326 at /news/ancient-rna-guided-system-could-simplify-delivery-gene-editing-therapies <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" class="datetime">April 3, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>A new computational approach eliminates time-intensive imaging, enabling high-resolution spatial mapping of gene expression in tissue.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" title="Thursday, April 3, 2025 - 05:00" class="datetime">April 3, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ffbkX92m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=8iiQYmFY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ChoROTIl 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc" alt="A spatial map of mouse embryo tissue with different colored dots representing cells." title="A spatial map of mouse embryo tissue with different colored dots representing cells." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Chenlei Hu, Chen lab </div> <div class="media-caption__description"> Spatial map of cell types in a mouse embryo. Each colored dot represents a different cell type. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/rss/news-blog-feed&amp;title=RSS%20Feed%20News%20%2B%20Blog" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> 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of how slide-DNA-seq &quot;sees&quot; cells' organization within a tumor." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/new-dna-sequencing-technique-preserves-cells%E2%80%99-locations-within-tissues" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">New DNA sequencing technique preserves cells’ locations within tissues</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/chemical-approach-imaging-cells-inside" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/chemical-approach-imaging-cells-inside"><picture> <source 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class="node__content"> <a href="/news/chemical-approach-imaging-cells-inside" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">A chemical approach to imaging cells from the inside</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Spatial transcriptomics technologies opened the door for new kinds of biological measurements, allowing scientists to generate detailed maps of where genes are expressed in tissue. But most methods rely on expensive and time-intensive imaging that requires specialized equipment.</p> <p>A new method developed by researchers at the ӳ����ý promises to make spatial transcriptomics easier for scientists to use. The approach eliminates the need for imaging and instead uses computational methods to reconstruct the spatial locations of gene expression. The team showed that by using their method, they could map larger sections of tissue more quickly and cheaply than with previous methods. They add that, more importantly, the new approach requires no specialized equipment and can be used by more researchers around the world. The work appears today in <em><a href="https://www.nature.com/articles/s41587-025-02612-0" target="_blank">Nature Biotechnology</a></em>.</p> <p>“Our work converts imaging into molecular biology — just a reaction in a test tube,” said <a href="/node/113836">Fei Chen</a>, who is a senior author on the study, a core institute member at the ӳ����ý, and an assistant professor in the Department of Stem Cell and Regenerative Biology at Harvard University. “That means anybody can use this approach if they have the algorithm and some common materials.”</p> <p>“When biologists think about spatial locations, they might think they need to look at samples with light microscopy or electron microscopy,” added Chenlei Hu. Hu is the first author on the work and a Harvard graduate student in Chen’s lab. “But we’ve found that we can computationally infer physical locations instead.”</p> <h2>Mapping with beads</h2> <p>The new findings build on a technique called <a href="https://www.science.org/doi/10.1126/science.aaw1219" target="_blank">Slide-seq</a>, which was developed by Chen, ӳ����ý core institute member <a href="/node/652411">Evan Macosko</a>, and colleagues in 2019. The method generates high-resolution maps of gene expression across tissue. Researchers first collect images of an array of DNA-barcoded beads on a slide, creating a reference that tells the location of each bead. Next, they place a tissue section on the beads and dissolve it, leaving messenger RNA from the tissue bound to the barcoded beads. They then load the beads into a sequencer and use specialized software to create a map of gene expression across the tissue.</p> <p>In the past, Chen’s lab made the arrays and imaged them for other scientists. Their microscope was under near-constant use. But lingering in their minds was the possibility that they could infer the location of each bead with sequencing alone, eliminating the need for imaging.&nbsp;</p> <p>They thought that if you knew the distance between every pair of beads on the array, you could reconstruct their spatial positions — in the same way you can locate a cell phone by knowing its distance from satellites.</p> <p>When she joined Chen’s lab, Hu thought it might be possible to pinpoint the location of the beads by measuring how much molecules diffuse between them. She and her colleagues built a new kind of bead array containing both “transmitter” and “receiver” beads, each with DNA barcodes. When exposed to UV light, the barcodes cleave from the transmitter beads, diffuse away, and are captured by the receiver beads. Receiver beads that are closer to transmitters will capture more DNA barcodes as they diffuse from the transmitters. Slide-seq’s sequencing step can measure the level of these captured barcodes, providing information not only about gene expression, but also the location of the beads. Hu then used an algorithm commonly used in single-cell analysis called Uniform Manifold Approximation and Projection (UMAP) to reconstruct the beads’ original locations on the slide.</p> <p>When the researchers used their method and the image-based Slide-seq to analyze the same sample, they found very little difference. Without the time-intensive imaging step, Chen’s team was able to map gene expression across larger sections of tissue than before: areas up to 1.2 centimeters wide of mouse embryo tissue (previous maps covered only about 3 millimeters). The Chen group is now working with the Macosko lab to map areas as large as 7 centimeters, close to the size of entire organs in people.</p> <p>“We’re no longer limited by how long it takes us to image something," Chen said. “Eventually we’d like to analyze the whole human brain. That just wasn’t possible with other technologies.”<br> &nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health (NHGRI) and the Opportunity Fund through the Technology Development Coordinating Center at Jackson Laboratories.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Hu, C et al. <a href="https://www.nature.com/articles/s41587-025-02612-0">Scalable spatial transcriptomics through computational array reconstruction</a>. <em>Nature Biotechnology</em>. Online April 3, 2025. DOI: 10.1038/s41587-025-02612-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/spatial-omics-0" hreflang="en">Spatial -omics</a></div> <div class="field__item"><a href="/broad-tags/evan-macosko" hreflang="en">Evan Macosko</a></div> <div class="field__item"><a href="/broad-tags/fei-chen" hreflang="en">Fei Chen</a></div> </div> </div> </div> </div> </div> Thu, 27 Feb 2025 15:21:20 +0000 Corie Lok 5558246 at /news/why-brain-cancer-often-resistant-immunotherapy <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" class="datetime">April 3, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>A new computational approach eliminates time-intensive imaging, enabling high-resolution spatial mapping of gene expression in tissue.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" title="Thursday, April 3, 2025 - 05:00" class="datetime">April 3, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ffbkX92m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=8iiQYmFY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ChoROTIl 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc" alt="A spatial map of mouse embryo tissue with different colored dots representing cells." title="A spatial map of mouse embryo tissue with different colored dots representing cells." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Chenlei Hu, Chen lab </div> <div class="media-caption__description"> Spatial map of cell types in a mouse embryo. Each colored dot represents a different cell type. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/rss/news-blog-feed&amp;title=RSS%20Feed%20News%20%2B%20Blog" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> 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field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/new-tool-uses-rna-sequencing-chart-rich-maps-cellular-and-tissue-function" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media 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of how slide-DNA-seq &quot;sees&quot; cells' organization within a tumor." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/new-dna-sequencing-technique-preserves-cells%E2%80%99-locations-within-tissues" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">New DNA sequencing technique preserves cells’ locations within tissues</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/chemical-approach-imaging-cells-inside" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/chemical-approach-imaging-cells-inside"><picture> <source 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class="node__content"> <a href="/news/chemical-approach-imaging-cells-inside" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">A chemical approach to imaging cells from the inside</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Spatial transcriptomics technologies opened the door for new kinds of biological measurements, allowing scientists to generate detailed maps of where genes are expressed in tissue. But most methods rely on expensive and time-intensive imaging that requires specialized equipment.</p> <p>A new method developed by researchers at the ӳ����ý promises to make spatial transcriptomics easier for scientists to use. The approach eliminates the need for imaging and instead uses computational methods to reconstruct the spatial locations of gene expression. The team showed that by using their method, they could map larger sections of tissue more quickly and cheaply than with previous methods. They add that, more importantly, the new approach requires no specialized equipment and can be used by more researchers around the world. The work appears today in <em><a href="https://www.nature.com/articles/s41587-025-02612-0" target="_blank">Nature Biotechnology</a></em>.</p> <p>“Our work converts imaging into molecular biology — just a reaction in a test tube,” said <a href="/node/113836">Fei Chen</a>, who is a senior author on the study, a core institute member at the ӳ����ý, and an assistant professor in the Department of Stem Cell and Regenerative Biology at Harvard University. “That means anybody can use this approach if they have the algorithm and some common materials.”</p> <p>“When biologists think about spatial locations, they might think they need to look at samples with light microscopy or electron microscopy,” added Chenlei Hu. Hu is the first author on the work and a Harvard graduate student in Chen’s lab. “But we’ve found that we can computationally infer physical locations instead.”</p> <h2>Mapping with beads</h2> <p>The new findings build on a technique called <a href="https://www.science.org/doi/10.1126/science.aaw1219" target="_blank">Slide-seq</a>, which was developed by Chen, ӳ����ý core institute member <a href="/node/652411">Evan Macosko</a>, and colleagues in 2019. The method generates high-resolution maps of gene expression across tissue. Researchers first collect images of an array of DNA-barcoded beads on a slide, creating a reference that tells the location of each bead. Next, they place a tissue section on the beads and dissolve it, leaving messenger RNA from the tissue bound to the barcoded beads. They then load the beads into a sequencer and use specialized software to create a map of gene expression across the tissue.</p> <p>In the past, Chen’s lab made the arrays and imaged them for other scientists. Their microscope was under near-constant use. But lingering in their minds was the possibility that they could infer the location of each bead with sequencing alone, eliminating the need for imaging.&nbsp;</p> <p>They thought that if you knew the distance between every pair of beads on the array, you could reconstruct their spatial positions — in the same way you can locate a cell phone by knowing its distance from satellites.</p> <p>When she joined Chen’s lab, Hu thought it might be possible to pinpoint the location of the beads by measuring how much molecules diffuse between them. She and her colleagues built a new kind of bead array containing both “transmitter” and “receiver” beads, each with DNA barcodes. When exposed to UV light, the barcodes cleave from the transmitter beads, diffuse away, and are captured by the receiver beads. Receiver beads that are closer to transmitters will capture more DNA barcodes as they diffuse from the transmitters. Slide-seq’s sequencing step can measure the level of these captured barcodes, providing information not only about gene expression, but also the location of the beads. Hu then used an algorithm commonly used in single-cell analysis called Uniform Manifold Approximation and Projection (UMAP) to reconstruct the beads’ original locations on the slide.</p> <p>When the researchers used their method and the image-based Slide-seq to analyze the same sample, they found very little difference. Without the time-intensive imaging step, Chen’s team was able to map gene expression across larger sections of tissue than before: areas up to 1.2 centimeters wide of mouse embryo tissue (previous maps covered only about 3 millimeters). The Chen group is now working with the Macosko lab to map areas as large as 7 centimeters, close to the size of entire organs in people.</p> <p>“We’re no longer limited by how long it takes us to image something," Chen said. “Eventually we’d like to analyze the whole human brain. That just wasn’t possible with other technologies.”<br> &nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health (NHGRI) and the Opportunity Fund through the Technology Development Coordinating Center at Jackson Laboratories.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Hu, C et al. <a href="https://www.nature.com/articles/s41587-025-02612-0">Scalable spatial transcriptomics through computational array reconstruction</a>. <em>Nature Biotechnology</em>. Online April 3, 2025. DOI: 10.1038/s41587-025-02612-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/spatial-omics-0" hreflang="en">Spatial -omics</a></div> <div class="field__item"><a href="/broad-tags/evan-macosko" hreflang="en">Evan Macosko</a></div> <div class="field__item"><a href="/broad-tags/fei-chen" hreflang="en">Fei Chen</a></div> </div> </div> </div> </div> </div> Wed, 26 Feb 2025 16:00:00 +0000 adicorat 5558236 at /news/alex-rives-joins-faculty-broad-institute-and-mit <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" class="datetime">April 3, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>A new computational approach eliminates time-intensive imaging, enabling high-resolution spatial mapping of gene expression in tissue.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" title="Thursday, April 3, 2025 - 05:00" class="datetime">April 3, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ffbkX92m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=8iiQYmFY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ChoROTIl 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc" alt="A spatial map of mouse embryo tissue with different colored dots representing cells." title="A spatial map of mouse embryo tissue with different colored dots representing cells." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Chenlei Hu, Chen lab </div> <div class="media-caption__description"> Spatial map of cell types in a mouse embryo. Each colored dot represents a different cell type. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/rss/news-blog-feed&amp;title=RSS%20Feed%20News%20%2B%20Blog" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> 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of how slide-DNA-seq &quot;sees&quot; cells' organization within a tumor." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/new-dna-sequencing-technique-preserves-cells%E2%80%99-locations-within-tissues" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">New DNA sequencing technique preserves cells’ locations within tissues</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/chemical-approach-imaging-cells-inside" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/chemical-approach-imaging-cells-inside"><picture> <source 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class="node__content"> <a href="/news/chemical-approach-imaging-cells-inside" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">A chemical approach to imaging cells from the inside</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Spatial transcriptomics technologies opened the door for new kinds of biological measurements, allowing scientists to generate detailed maps of where genes are expressed in tissue. But most methods rely on expensive and time-intensive imaging that requires specialized equipment.</p> <p>A new method developed by researchers at the ӳ����ý promises to make spatial transcriptomics easier for scientists to use. The approach eliminates the need for imaging and instead uses computational methods to reconstruct the spatial locations of gene expression. The team showed that by using their method, they could map larger sections of tissue more quickly and cheaply than with previous methods. They add that, more importantly, the new approach requires no specialized equipment and can be used by more researchers around the world. The work appears today in <em><a href="https://www.nature.com/articles/s41587-025-02612-0" target="_blank">Nature Biotechnology</a></em>.</p> <p>“Our work converts imaging into molecular biology — just a reaction in a test tube,” said <a href="/node/113836">Fei Chen</a>, who is a senior author on the study, a core institute member at the ӳ����ý, and an assistant professor in the Department of Stem Cell and Regenerative Biology at Harvard University. “That means anybody can use this approach if they have the algorithm and some common materials.”</p> <p>“When biologists think about spatial locations, they might think they need to look at samples with light microscopy or electron microscopy,” added Chenlei Hu. Hu is the first author on the work and a Harvard graduate student in Chen’s lab. “But we’ve found that we can computationally infer physical locations instead.”</p> <h2>Mapping with beads</h2> <p>The new findings build on a technique called <a href="https://www.science.org/doi/10.1126/science.aaw1219" target="_blank">Slide-seq</a>, which was developed by Chen, ӳ����ý core institute member <a href="/node/652411">Evan Macosko</a>, and colleagues in 2019. The method generates high-resolution maps of gene expression across tissue. Researchers first collect images of an array of DNA-barcoded beads on a slide, creating a reference that tells the location of each bead. Next, they place a tissue section on the beads and dissolve it, leaving messenger RNA from the tissue bound to the barcoded beads. They then load the beads into a sequencer and use specialized software to create a map of gene expression across the tissue.</p> <p>In the past, Chen’s lab made the arrays and imaged them for other scientists. Their microscope was under near-constant use. But lingering in their minds was the possibility that they could infer the location of each bead with sequencing alone, eliminating the need for imaging.&nbsp;</p> <p>They thought that if you knew the distance between every pair of beads on the array, you could reconstruct their spatial positions — in the same way you can locate a cell phone by knowing its distance from satellites.</p> <p>When she joined Chen’s lab, Hu thought it might be possible to pinpoint the location of the beads by measuring how much molecules diffuse between them. She and her colleagues built a new kind of bead array containing both “transmitter” and “receiver” beads, each with DNA barcodes. When exposed to UV light, the barcodes cleave from the transmitter beads, diffuse away, and are captured by the receiver beads. Receiver beads that are closer to transmitters will capture more DNA barcodes as they diffuse from the transmitters. Slide-seq’s sequencing step can measure the level of these captured barcodes, providing information not only about gene expression, but also the location of the beads. Hu then used an algorithm commonly used in single-cell analysis called Uniform Manifold Approximation and Projection (UMAP) to reconstruct the beads’ original locations on the slide.</p> <p>When the researchers used their method and the image-based Slide-seq to analyze the same sample, they found very little difference. Without the time-intensive imaging step, Chen’s team was able to map gene expression across larger sections of tissue than before: areas up to 1.2 centimeters wide of mouse embryo tissue (previous maps covered only about 3 millimeters). The Chen group is now working with the Macosko lab to map areas as large as 7 centimeters, close to the size of entire organs in people.</p> <p>“We’re no longer limited by how long it takes us to image something," Chen said. “Eventually we’d like to analyze the whole human brain. That just wasn’t possible with other technologies.”<br> &nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health (NHGRI) and the Opportunity Fund through the Technology Development Coordinating Center at Jackson Laboratories.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Hu, C et al. <a href="https://www.nature.com/articles/s41587-025-02612-0">Scalable spatial transcriptomics through computational array reconstruction</a>. <em>Nature Biotechnology</em>. Online April 3, 2025. DOI: 10.1038/s41587-025-02612-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/spatial-omics-0" hreflang="en">Spatial -omics</a></div> <div class="field__item"><a href="/broad-tags/evan-macosko" hreflang="en">Evan Macosko</a></div> <div class="field__item"><a href="/broad-tags/fei-chen" hreflang="en">Fei Chen</a></div> </div> </div> </div> </div> </div> Tue, 18 Feb 2025 14:08:54 +0000 leah@broadinstitute.org 5558226 at /news/mapping-mrna-through-its-life-cycle-within-cell <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" class="datetime">April 3, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists have developed a way to scale up spatial genomics and lower costs</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>A new computational approach eliminates time-intensive imaging, enabling high-resolution spatial mapping of gene expression in tissue.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-04-03T05:00:00-04:00" title="Thursday, April 3, 2025 - 05:00" class="datetime">April 3, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=Xb1CWUcE 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ffbkX92m 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=8iiQYmFY 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=ChoROTIl 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/NBT_Chen_main_cropped.png?h=11af8684&amp;itok=wIXX7GQc" alt="A spatial map of mouse embryo tissue with different colored dots representing cells." title="A spatial map of mouse embryo tissue with different colored dots representing cells." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Chenlei Hu, Chen lab </div> <div class="media-caption__description"> Spatial map of cell types in a mouse embryo. Each colored dot represents a different cell type. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/rss/news-blog-feed&amp;title=RSS%20Feed%20News%20%2B%20Blog" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> 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of how slide-DNA-seq &quot;sees&quot; cells' organization within a tumor." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/new-dna-sequencing-technique-preserves-cells%E2%80%99-locations-within-tissues" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">New DNA sequencing technique preserves cells’ locations within tissues</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/chemical-approach-imaging-cells-inside" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/chemical-approach-imaging-cells-inside"><picture> <source 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class="node__content"> <a href="/news/chemical-approach-imaging-cells-inside" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">A chemical approach to imaging cells from the inside</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Spatial transcriptomics technologies opened the door for new kinds of biological measurements, allowing scientists to generate detailed maps of where genes are expressed in tissue. But most methods rely on expensive and time-intensive imaging that requires specialized equipment.</p> <p>A new method developed by researchers at the ӳ����ý promises to make spatial transcriptomics easier for scientists to use. The approach eliminates the need for imaging and instead uses computational methods to reconstruct the spatial locations of gene expression. The team showed that by using their method, they could map larger sections of tissue more quickly and cheaply than with previous methods. They add that, more importantly, the new approach requires no specialized equipment and can be used by more researchers around the world. The work appears today in <em><a href="https://www.nature.com/articles/s41587-025-02612-0" target="_blank">Nature Biotechnology</a></em>.</p> <p>“Our work converts imaging into molecular biology — just a reaction in a test tube,” said <a href="/node/113836">Fei Chen</a>, who is a senior author on the study, a core institute member at the ӳ����ý, and an assistant professor in the Department of Stem Cell and Regenerative Biology at Harvard University. “That means anybody can use this approach if they have the algorithm and some common materials.”</p> <p>“When biologists think about spatial locations, they might think they need to look at samples with light microscopy or electron microscopy,” added Chenlei Hu. Hu is the first author on the work and a Harvard graduate student in Chen’s lab. “But we’ve found that we can computationally infer physical locations instead.”</p> <h2>Mapping with beads</h2> <p>The new findings build on a technique called <a href="https://www.science.org/doi/10.1126/science.aaw1219" target="_blank">Slide-seq</a>, which was developed by Chen, ӳ����ý core institute member <a href="/node/652411">Evan Macosko</a>, and colleagues in 2019. The method generates high-resolution maps of gene expression across tissue. Researchers first collect images of an array of DNA-barcoded beads on a slide, creating a reference that tells the location of each bead. Next, they place a tissue section on the beads and dissolve it, leaving messenger RNA from the tissue bound to the barcoded beads. They then load the beads into a sequencer and use specialized software to create a map of gene expression across the tissue.</p> <p>In the past, Chen’s lab made the arrays and imaged them for other scientists. Their microscope was under near-constant use. But lingering in their minds was the possibility that they could infer the location of each bead with sequencing alone, eliminating the need for imaging.&nbsp;</p> <p>They thought that if you knew the distance between every pair of beads on the array, you could reconstruct their spatial positions — in the same way you can locate a cell phone by knowing its distance from satellites.</p> <p>When she joined Chen’s lab, Hu thought it might be possible to pinpoint the location of the beads by measuring how much molecules diffuse between them. She and her colleagues built a new kind of bead array containing both “transmitter” and “receiver” beads, each with DNA barcodes. When exposed to UV light, the barcodes cleave from the transmitter beads, diffuse away, and are captured by the receiver beads. Receiver beads that are closer to transmitters will capture more DNA barcodes as they diffuse from the transmitters. Slide-seq’s sequencing step can measure the level of these captured barcodes, providing information not only about gene expression, but also the location of the beads. Hu then used an algorithm commonly used in single-cell analysis called Uniform Manifold Approximation and Projection (UMAP) to reconstruct the beads’ original locations on the slide.</p> <p>When the researchers used their method and the image-based Slide-seq to analyze the same sample, they found very little difference. Without the time-intensive imaging step, Chen’s team was able to map gene expression across larger sections of tissue than before: areas up to 1.2 centimeters wide of mouse embryo tissue (previous maps covered only about 3 millimeters). The Chen group is now working with the Macosko lab to map areas as large as 7 centimeters, close to the size of entire organs in people.</p> <p>“We’re no longer limited by how long it takes us to image something," Chen said. “Eventually we’d like to analyze the whole human brain. That just wasn’t possible with other technologies.”<br> &nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the National Institutes of Health (NHGRI) and the Opportunity Fund through the Technology Development Coordinating Center at Jackson Laboratories.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Hu, C et al. <a href="https://www.nature.com/articles/s41587-025-02612-0">Scalable spatial transcriptomics through computational array reconstruction</a>. <em>Nature Biotechnology</em>. Online April 3, 2025. DOI: 10.1038/s41587-025-02612-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/spatial-omics-0" hreflang="en">Spatial -omics</a></div> <div class="field__item"><a href="/broad-tags/evan-macosko" hreflang="en">Evan Macosko</a></div> <div class="field__item"><a href="/broad-tags/fei-chen" hreflang="en">Fei Chen</a></div> </div> </div> </div> </div> </div> Tue, 11 Feb 2025 15:56:48 +0000 Corie Lok 5558216 at