/ en /news/scientists-find-region-mouse-gut-tightly-regulated-immune-system <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists find a region of the mouse gut tightly regulated by the immune system</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="2024-11-20T11:00:00-05:00" class="datetime">November 20, 2024</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> <li> <a href="/news">News</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 find a region of the mouse gut tightly regulated by the immune system</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 spatial map of gene expression across the intestine reveals the organ’s remarkable adaptability.</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="2024-11-20T11:00:00-05:00" title="Wednesday, November 20, 2024 - 11:00" class="datetime">November 20, 2024</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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=-uwKD0TI 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=-uwKD0TI 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=X1PLTXrA 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=UMAllycL 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=FFALKwIi 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=c6Smt5Zh 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/longstory/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=c6Smt5Zh" width="499" height="294" alt="A spatial map of colon tissue with colored dots showing different cell types." title="A spatial map of colon tissue with colored dots showing different cell types." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Xavier lab </div> <div class="media-caption__description"> A map showing the distribution of different structural cell types in the colon. Fibroblasts are labeled in red, enterocytes in blue, and goblet cells in yellow. </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=/taxonomy/term/1526/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg 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> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/1526/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/1526/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field 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-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The intestine maintains a delicate balance in the body, absorbing nutrients and water while maintaining a healthy relationship with the gut microbiome, but this equilibrium is disrupted in parts of the intestine in conditions such as celiac disease, ulcerative colitis, and Crohn’s disease. Scientists don’t fully understand how different regions of the organ resist or adapt to changes in the environment and how that is disrupted in disease.</p> <p>Now, researchers at the ӳ����ý of MIT and Harvard and Massachusetts General Hospital have analyzed the entire mouse intestine, mapping gene expression and cell states and location in the healthy gut and in response to perturbations such as inflammation. They identified tight regulation of cell types and states in different regions of the organ, as well as a unique segment of the colon that is controlled by immune signals. The findings, which appear today in <em><a href="https://www.nature.com/articles/s41586-024-08216-z" target="_blank">Nature</a></em>, reveal the surprising adaptability and resilience of the intestine to perturbations and highlight the importance of considering how cell processes are regulated and vary across different parts of a tissue or organ.</p> <p>“The intestine and in particular the colon has been studied for decades but it hasn’t been characterized in this way before, and that both forces us to reevaluate many different studies and opens up a window for future research,” said Toufic Mayassi, a co-first author on the study along with Chenhao Li. Mayassi and Li are postdoctoral researchers in the lab of Ramnik Xavier, who is a core institute member at the ӳ����ý, member of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH), and senior author of the study.&nbsp;</p> <p>“This work illustrates that you really have to integrate the spatial relationships governing a given organ into your thinking, and we hope our study provides a platform and framework that helps put both previous and future discoveries in context,” Mayassi said.</p> <p><a href="http://www.broadinstitute.org/node/4721/">Xavier</a> is the director of ӳ����ý’s Immunology Program, as well as the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, director of the Center for Computational and Integrative Biology and member of the Department of Molecular Biology at MGH, and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.</p> <p>“We’ve built a blueprint of the entire gut, and that’s a remarkable achievement,” said Xavier. “We now have a way of studying the whole organ, examining the effect of genetic variants and immune responses associated with diet, the microbiome, and gastrointestinal disease, and designing many other experiments.”</p> <h2>Mapping the intestine</h2> <p>Many previous studies of the gut looked at cells or organ-like assemblies of cells in a dish. While such approaches provide a controlled environment to study the function of specific genetic variants involved in disease, they don’t illustrate how cells from different parts of an intact organ interact to bring about disease.</p> <p>In 2021, Mayassi, who spent his PhD studying immune responses in the intestine, teamed up with Li, a computational biologist, to build a comprehensive map of gene expression across the entire mouse small intestine and colon using spatial transcriptomics and computational approaches.&nbsp;</p> <p>To the researchers’ surprise, the spatial composition of the intestine — the relative location of various cell types and the genes they express — remained relatively stable when certain factors changed. It stayed the same in animals with and without gut microbiota and in tissue collected at night or during the day, suggesting that neither the microbiome nor circadian rhythms impacted the spatial landscape.&nbsp;</p> <p>The intestine also showed signs of resilience. When Mayassi treated the animals with a molecule known to induce inflammation, gene expression and cell spatial distribution changed but showed signs of returning to normal a month later, and had almost entirely recovered by three months. The findings suggest that the gut’s ability to bounce back from changes brought about by inflammation could be critical to intestinal health and function.&nbsp;</p> <p>“As a computational biologist, it is exciting to be involved in generating and exploring such a unique dataset,” Li said. “It opens the door to developing tools for analyzing spatial data and informs the design of future studies on the small and large intestine.”</p> <h2>Immune control</h2> <p>Though the intestine was stable to many influences, unique niches within the organ were affected by the gut microbiota and showed signs of adaptation. Mice that had a normal microbiome expressed unique genes in a specific region of the colon compared to germ-free mice. Using single-cell RNA sequencing, the authors found that the changes occurred in three structural cell types. In particular, goblet cells — cup-shaped cells that secrete mucus — expressed those genes only in the presence of ILC2s, a kind of immune cell.</p> <p>Next, the researchers plan to apply their method to study how other factors including sex, diet, food allergies, and genetic risk factors for conditions such as inflammatory bowel disease impact the intestine’s spatial landscape. They also hope to elucidate the extent to which the findings in mice correlate with spatial control in the human gut.</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 Center for the Study of Inflammatory Bowel Disease, National Institutes of Health, The Leona M. and Harry B. Helmsley Charitable Trust, the Klarman Cell Observatory, the Jill Roberts Institute for Research in IBD, Kenneth Rainin Foundation, the Sanders Family Foundation, Rosanne H. Silbermann Foundation, Linda and Glenn Greenberg, the Allen Discovery Center Program, and Paul G. Allen Frontiers Group advised program of the Paul G. Allen Family Foundation.</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>Mayassi T, Li C, et al. <a href="https://www.nature.com/articles/s41586-024-08216-z" target="_blank">Spatially restricted immune and microbiota-driven adaptation of the gut</a>. <em>Nature</em>. Online November 20, 2024. DOI: 10.1038/s41586-024-08216-z.</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/immunology-program" hreflang="en">Immunology Program</a></div> <div class="field__item"><a href="/broad-tags/xavier-lab" hreflang="en">Xavier Lab</a></div> <div class="field__item"><a href="/broad-tags/spatial-omics-0" hreflang="en">Spatial -omics</a></div> </div> </div> </div> </div> </div> Wed, 20 Nov 2024 16:00:00 +0000 adicorat 5557901 at /news/researchers-identify-gut-microbiome-signatures-linked-precancerous-colon-polyps <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists find a region of the mouse gut tightly regulated by the immune system</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="2024-11-20T11:00:00-05:00" class="datetime">November 20, 2024</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> <li> <a href="/news">News</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 find a region of the mouse gut tightly regulated by the immune system</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 spatial map of gene expression across the intestine reveals the organ’s remarkable adaptability.</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="2024-11-20T11:00:00-05:00" title="Wednesday, November 20, 2024 - 11:00" class="datetime">November 20, 2024</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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=-uwKD0TI 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=-uwKD0TI 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=X1PLTXrA 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=UMAllycL 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=FFALKwIi 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=c6Smt5Zh 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/longstory/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=c6Smt5Zh" width="499" height="294" alt="A spatial map of colon tissue with colored dots showing different cell types." title="A spatial map of colon tissue with colored dots showing different cell types." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Xavier lab </div> <div class="media-caption__description"> A map showing the distribution of different structural cell types in the colon. Fibroblasts are labeled in red, enterocytes in blue, and goblet cells in yellow. </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=/taxonomy/term/1526/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg 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> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/1526/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/1526/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field 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-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The intestine maintains a delicate balance in the body, absorbing nutrients and water while maintaining a healthy relationship with the gut microbiome, but this equilibrium is disrupted in parts of the intestine in conditions such as celiac disease, ulcerative colitis, and Crohn’s disease. Scientists don’t fully understand how different regions of the organ resist or adapt to changes in the environment and how that is disrupted in disease.</p> <p>Now, researchers at the ӳ����ý of MIT and Harvard and Massachusetts General Hospital have analyzed the entire mouse intestine, mapping gene expression and cell states and location in the healthy gut and in response to perturbations such as inflammation. They identified tight regulation of cell types and states in different regions of the organ, as well as a unique segment of the colon that is controlled by immune signals. The findings, which appear today in <em><a href="https://www.nature.com/articles/s41586-024-08216-z" target="_blank">Nature</a></em>, reveal the surprising adaptability and resilience of the intestine to perturbations and highlight the importance of considering how cell processes are regulated and vary across different parts of a tissue or organ.</p> <p>“The intestine and in particular the colon has been studied for decades but it hasn’t been characterized in this way before, and that both forces us to reevaluate many different studies and opens up a window for future research,” said Toufic Mayassi, a co-first author on the study along with Chenhao Li. Mayassi and Li are postdoctoral researchers in the lab of Ramnik Xavier, who is a core institute member at the ӳ����ý, member of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH), and senior author of the study.&nbsp;</p> <p>“This work illustrates that you really have to integrate the spatial relationships governing a given organ into your thinking, and we hope our study provides a platform and framework that helps put both previous and future discoveries in context,” Mayassi said.</p> <p><a href="http://www.broadinstitute.org/node/4721/">Xavier</a> is the director of ӳ����ý’s Immunology Program, as well as the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, director of the Center for Computational and Integrative Biology and member of the Department of Molecular Biology at MGH, and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.</p> <p>“We’ve built a blueprint of the entire gut, and that’s a remarkable achievement,” said Xavier. “We now have a way of studying the whole organ, examining the effect of genetic variants and immune responses associated with diet, the microbiome, and gastrointestinal disease, and designing many other experiments.”</p> <h2>Mapping the intestine</h2> <p>Many previous studies of the gut looked at cells or organ-like assemblies of cells in a dish. While such approaches provide a controlled environment to study the function of specific genetic variants involved in disease, they don’t illustrate how cells from different parts of an intact organ interact to bring about disease.</p> <p>In 2021, Mayassi, who spent his PhD studying immune responses in the intestine, teamed up with Li, a computational biologist, to build a comprehensive map of gene expression across the entire mouse small intestine and colon using spatial transcriptomics and computational approaches.&nbsp;</p> <p>To the researchers’ surprise, the spatial composition of the intestine — the relative location of various cell types and the genes they express — remained relatively stable when certain factors changed. It stayed the same in animals with and without gut microbiota and in tissue collected at night or during the day, suggesting that neither the microbiome nor circadian rhythms impacted the spatial landscape.&nbsp;</p> <p>The intestine also showed signs of resilience. When Mayassi treated the animals with a molecule known to induce inflammation, gene expression and cell spatial distribution changed but showed signs of returning to normal a month later, and had almost entirely recovered by three months. The findings suggest that the gut’s ability to bounce back from changes brought about by inflammation could be critical to intestinal health and function.&nbsp;</p> <p>“As a computational biologist, it is exciting to be involved in generating and exploring such a unique dataset,” Li said. “It opens the door to developing tools for analyzing spatial data and informs the design of future studies on the small and large intestine.”</p> <h2>Immune control</h2> <p>Though the intestine was stable to many influences, unique niches within the organ were affected by the gut microbiota and showed signs of adaptation. Mice that had a normal microbiome expressed unique genes in a specific region of the colon compared to germ-free mice. Using single-cell RNA sequencing, the authors found that the changes occurred in three structural cell types. In particular, goblet cells — cup-shaped cells that secrete mucus — expressed those genes only in the presence of ILC2s, a kind of immune cell.</p> <p>Next, the researchers plan to apply their method to study how other factors including sex, diet, food allergies, and genetic risk factors for conditions such as inflammatory bowel disease impact the intestine’s spatial landscape. They also hope to elucidate the extent to which the findings in mice correlate with spatial control in the human gut.</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 Center for the Study of Inflammatory Bowel Disease, National Institutes of Health, The Leona M. and Harry B. Helmsley Charitable Trust, the Klarman Cell Observatory, the Jill Roberts Institute for Research in IBD, Kenneth Rainin Foundation, the Sanders Family Foundation, Rosanne H. Silbermann Foundation, Linda and Glenn Greenberg, the Allen Discovery Center Program, and Paul G. Allen Frontiers Group advised program of the Paul G. Allen Family Foundation.</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>Mayassi T, Li C, et al. <a href="https://www.nature.com/articles/s41586-024-08216-z" target="_blank">Spatially restricted immune and microbiota-driven adaptation of the gut</a>. <em>Nature</em>. Online November 20, 2024. DOI: 10.1038/s41586-024-08216-z.</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/immunology-program" hreflang="en">Immunology Program</a></div> <div class="field__item"><a href="/broad-tags/xavier-lab" hreflang="en">Xavier Lab</a></div> <div class="field__item"><a href="/broad-tags/spatial-omics-0" hreflang="en">Spatial -omics</a></div> </div> </div> </div> </div> </div> Wed, 14 Jun 2023 12:59:00 +0000 tulrich@broadinstitute.org 1282366 at /news/broad-discovery-center-cambridge-opens-public-october <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists find a region of the mouse gut tightly regulated by the immune system</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="2024-11-20T11:00:00-05:00" class="datetime">November 20, 2024</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> <li> <a href="/news">News</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 find a region of the mouse gut tightly regulated by the immune system</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 spatial map of gene expression across the intestine reveals the organ’s remarkable adaptability.</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="2024-11-20T11:00:00-05:00" title="Wednesday, November 20, 2024 - 11:00" class="datetime">November 20, 2024</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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=-uwKD0TI 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=-uwKD0TI 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=X1PLTXrA 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=UMAllycL 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=FFALKwIi 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=c6Smt5Zh 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/longstory/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=c6Smt5Zh" width="499" height="294" alt="A spatial map of colon tissue with colored dots showing different cell types." title="A spatial map of colon tissue with colored dots showing different cell types." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Xavier lab </div> <div class="media-caption__description"> A map showing the distribution of different structural cell types in the colon. Fibroblasts are labeled in red, enterocytes in blue, and goblet cells in yellow. </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=/taxonomy/term/1526/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg 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> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/1526/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/1526/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field 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-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The intestine maintains a delicate balance in the body, absorbing nutrients and water while maintaining a healthy relationship with the gut microbiome, but this equilibrium is disrupted in parts of the intestine in conditions such as celiac disease, ulcerative colitis, and Crohn’s disease. Scientists don’t fully understand how different regions of the organ resist or adapt to changes in the environment and how that is disrupted in disease.</p> <p>Now, researchers at the ӳ����ý of MIT and Harvard and Massachusetts General Hospital have analyzed the entire mouse intestine, mapping gene expression and cell states and location in the healthy gut and in response to perturbations such as inflammation. They identified tight regulation of cell types and states in different regions of the organ, as well as a unique segment of the colon that is controlled by immune signals. The findings, which appear today in <em><a href="https://www.nature.com/articles/s41586-024-08216-z" target="_blank">Nature</a></em>, reveal the surprising adaptability and resilience of the intestine to perturbations and highlight the importance of considering how cell processes are regulated and vary across different parts of a tissue or organ.</p> <p>“The intestine and in particular the colon has been studied for decades but it hasn’t been characterized in this way before, and that both forces us to reevaluate many different studies and opens up a window for future research,” said Toufic Mayassi, a co-first author on the study along with Chenhao Li. Mayassi and Li are postdoctoral researchers in the lab of Ramnik Xavier, who is a core institute member at the ӳ����ý, member of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH), and senior author of the study.&nbsp;</p> <p>“This work illustrates that you really have to integrate the spatial relationships governing a given organ into your thinking, and we hope our study provides a platform and framework that helps put both previous and future discoveries in context,” Mayassi said.</p> <p><a href="http://www.broadinstitute.org/node/4721/">Xavier</a> is the director of ӳ����ý’s Immunology Program, as well as the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, director of the Center for Computational and Integrative Biology and member of the Department of Molecular Biology at MGH, and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.</p> <p>“We’ve built a blueprint of the entire gut, and that’s a remarkable achievement,” said Xavier. “We now have a way of studying the whole organ, examining the effect of genetic variants and immune responses associated with diet, the microbiome, and gastrointestinal disease, and designing many other experiments.”</p> <h2>Mapping the intestine</h2> <p>Many previous studies of the gut looked at cells or organ-like assemblies of cells in a dish. While such approaches provide a controlled environment to study the function of specific genetic variants involved in disease, they don’t illustrate how cells from different parts of an intact organ interact to bring about disease.</p> <p>In 2021, Mayassi, who spent his PhD studying immune responses in the intestine, teamed up with Li, a computational biologist, to build a comprehensive map of gene expression across the entire mouse small intestine and colon using spatial transcriptomics and computational approaches.&nbsp;</p> <p>To the researchers’ surprise, the spatial composition of the intestine — the relative location of various cell types and the genes they express — remained relatively stable when certain factors changed. It stayed the same in animals with and without gut microbiota and in tissue collected at night or during the day, suggesting that neither the microbiome nor circadian rhythms impacted the spatial landscape.&nbsp;</p> <p>The intestine also showed signs of resilience. When Mayassi treated the animals with a molecule known to induce inflammation, gene expression and cell spatial distribution changed but showed signs of returning to normal a month later, and had almost entirely recovered by three months. The findings suggest that the gut’s ability to bounce back from changes brought about by inflammation could be critical to intestinal health and function.&nbsp;</p> <p>“As a computational biologist, it is exciting to be involved in generating and exploring such a unique dataset,” Li said. “It opens the door to developing tools for analyzing spatial data and informs the design of future studies on the small and large intestine.”</p> <h2>Immune control</h2> <p>Though the intestine was stable to many influences, unique niches within the organ were affected by the gut microbiota and showed signs of adaptation. Mice that had a normal microbiome expressed unique genes in a specific region of the colon compared to germ-free mice. Using single-cell RNA sequencing, the authors found that the changes occurred in three structural cell types. In particular, goblet cells — cup-shaped cells that secrete mucus — expressed those genes only in the presence of ILC2s, a kind of immune cell.</p> <p>Next, the researchers plan to apply their method to study how other factors including sex, diet, food allergies, and genetic risk factors for conditions such as inflammatory bowel disease impact the intestine’s spatial landscape. They also hope to elucidate the extent to which the findings in mice correlate with spatial control in the human gut.</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 Center for the Study of Inflammatory Bowel Disease, National Institutes of Health, The Leona M. and Harry B. Helmsley Charitable Trust, the Klarman Cell Observatory, the Jill Roberts Institute for Research in IBD, Kenneth Rainin Foundation, the Sanders Family Foundation, Rosanne H. Silbermann Foundation, Linda and Glenn Greenberg, the Allen Discovery Center Program, and Paul G. Allen Frontiers Group advised program of the Paul G. Allen Family Foundation.</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>Mayassi T, Li C, et al. <a href="https://www.nature.com/articles/s41586-024-08216-z" target="_blank">Spatially restricted immune and microbiota-driven adaptation of the gut</a>. <em>Nature</em>. Online November 20, 2024. DOI: 10.1038/s41586-024-08216-z.</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/immunology-program" hreflang="en">Immunology Program</a></div> <div class="field__item"><a href="/broad-tags/xavier-lab" hreflang="en">Xavier Lab</a></div> <div class="field__item"><a href="/broad-tags/spatial-omics-0" hreflang="en">Spatial -omics</a></div> </div> </div> </div> </div> </div> Mon, 19 Sep 2022 14:53:09 +0000 kzusi@broadinstitute.org 1195701 at /news/untangling-immune-response-vaccines <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists find a region of the mouse gut tightly regulated by the immune system</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="2024-11-20T11:00:00-05:00" class="datetime">November 20, 2024</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> <li> <a href="/news">News</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 find a region of the mouse gut tightly regulated by the immune system</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 spatial map of gene expression across the intestine reveals the organ’s remarkable adaptability.</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="2024-11-20T11:00:00-05:00" title="Wednesday, November 20, 2024 - 11:00" class="datetime">November 20, 2024</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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=-uwKD0TI 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=-uwKD0TI 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=X1PLTXrA 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=UMAllycL 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=FFALKwIi 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=c6Smt5Zh 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/longstory/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=c6Smt5Zh" width="499" height="294" alt="A spatial map of colon tissue with colored dots showing different cell types." title="A spatial map of colon tissue with colored dots showing different cell types." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Xavier lab </div> <div class="media-caption__description"> A map showing the distribution of different structural cell types in the colon. Fibroblasts are labeled in red, enterocytes in blue, and goblet cells in yellow. </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=/taxonomy/term/1526/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg 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> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/1526/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/1526/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field 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-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The intestine maintains a delicate balance in the body, absorbing nutrients and water while maintaining a healthy relationship with the gut microbiome, but this equilibrium is disrupted in parts of the intestine in conditions such as celiac disease, ulcerative colitis, and Crohn’s disease. Scientists don’t fully understand how different regions of the organ resist or adapt to changes in the environment and how that is disrupted in disease.</p> <p>Now, researchers at the ӳ����ý of MIT and Harvard and Massachusetts General Hospital have analyzed the entire mouse intestine, mapping gene expression and cell states and location in the healthy gut and in response to perturbations such as inflammation. They identified tight regulation of cell types and states in different regions of the organ, as well as a unique segment of the colon that is controlled by immune signals. The findings, which appear today in <em><a href="https://www.nature.com/articles/s41586-024-08216-z" target="_blank">Nature</a></em>, reveal the surprising adaptability and resilience of the intestine to perturbations and highlight the importance of considering how cell processes are regulated and vary across different parts of a tissue or organ.</p> <p>“The intestine and in particular the colon has been studied for decades but it hasn’t been characterized in this way before, and that both forces us to reevaluate many different studies and opens up a window for future research,” said Toufic Mayassi, a co-first author on the study along with Chenhao Li. Mayassi and Li are postdoctoral researchers in the lab of Ramnik Xavier, who is a core institute member at the ӳ����ý, member of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH), and senior author of the study.&nbsp;</p> <p>“This work illustrates that you really have to integrate the spatial relationships governing a given organ into your thinking, and we hope our study provides a platform and framework that helps put both previous and future discoveries in context,” Mayassi said.</p> <p><a href="http://www.broadinstitute.org/node/4721/">Xavier</a> is the director of ӳ����ý’s Immunology Program, as well as the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, director of the Center for Computational and Integrative Biology and member of the Department of Molecular Biology at MGH, and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.</p> <p>“We’ve built a blueprint of the entire gut, and that’s a remarkable achievement,” said Xavier. “We now have a way of studying the whole organ, examining the effect of genetic variants and immune responses associated with diet, the microbiome, and gastrointestinal disease, and designing many other experiments.”</p> <h2>Mapping the intestine</h2> <p>Many previous studies of the gut looked at cells or organ-like assemblies of cells in a dish. While such approaches provide a controlled environment to study the function of specific genetic variants involved in disease, they don’t illustrate how cells from different parts of an intact organ interact to bring about disease.</p> <p>In 2021, Mayassi, who spent his PhD studying immune responses in the intestine, teamed up with Li, a computational biologist, to build a comprehensive map of gene expression across the entire mouse small intestine and colon using spatial transcriptomics and computational approaches.&nbsp;</p> <p>To the researchers’ surprise, the spatial composition of the intestine — the relative location of various cell types and the genes they express — remained relatively stable when certain factors changed. It stayed the same in animals with and without gut microbiota and in tissue collected at night or during the day, suggesting that neither the microbiome nor circadian rhythms impacted the spatial landscape.&nbsp;</p> <p>The intestine also showed signs of resilience. When Mayassi treated the animals with a molecule known to induce inflammation, gene expression and cell spatial distribution changed but showed signs of returning to normal a month later, and had almost entirely recovered by three months. The findings suggest that the gut’s ability to bounce back from changes brought about by inflammation could be critical to intestinal health and function.&nbsp;</p> <p>“As a computational biologist, it is exciting to be involved in generating and exploring such a unique dataset,” Li said. “It opens the door to developing tools for analyzing spatial data and informs the design of future studies on the small and large intestine.”</p> <h2>Immune control</h2> <p>Though the intestine was stable to many influences, unique niches within the organ were affected by the gut microbiota and showed signs of adaptation. Mice that had a normal microbiome expressed unique genes in a specific region of the colon compared to germ-free mice. Using single-cell RNA sequencing, the authors found that the changes occurred in three structural cell types. In particular, goblet cells — cup-shaped cells that secrete mucus — expressed those genes only in the presence of ILC2s, a kind of immune cell.</p> <p>Next, the researchers plan to apply their method to study how other factors including sex, diet, food allergies, and genetic risk factors for conditions such as inflammatory bowel disease impact the intestine’s spatial landscape. They also hope to elucidate the extent to which the findings in mice correlate with spatial control in the human gut.</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 Center for the Study of Inflammatory Bowel Disease, National Institutes of Health, The Leona M. and Harry B. Helmsley Charitable Trust, the Klarman Cell Observatory, the Jill Roberts Institute for Research in IBD, Kenneth Rainin Foundation, the Sanders Family Foundation, Rosanne H. Silbermann Foundation, Linda and Glenn Greenberg, the Allen Discovery Center Program, and Paul G. Allen Frontiers Group advised program of the Paul G. Allen Family Foundation.</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>Mayassi T, Li C, et al. <a href="https://www.nature.com/articles/s41586-024-08216-z" target="_blank">Spatially restricted immune and microbiota-driven adaptation of the gut</a>. <em>Nature</em>. Online November 20, 2024. DOI: 10.1038/s41586-024-08216-z.</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/immunology-program" hreflang="en">Immunology Program</a></div> <div class="field__item"><a href="/broad-tags/xavier-lab" hreflang="en">Xavier Lab</a></div> <div class="field__item"><a href="/broad-tags/spatial-omics-0" hreflang="en">Spatial -omics</a></div> </div> </div> </div> </div> </div> Thu, 02 Dec 2021 17:13:02 +0000 adicorat 1126841 at /news/single-cell-atlas-nerve-cells-gut-reveals-web-connections <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists find a region of the mouse gut tightly regulated by the immune system</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="2024-11-20T11:00:00-05:00" class="datetime">November 20, 2024</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> <li> <a href="/news">News</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 find a region of the mouse gut tightly regulated by the immune system</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 spatial map of gene expression across the intestine reveals the organ’s remarkable adaptability.</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="2024-11-20T11:00:00-05:00" title="Wednesday, November 20, 2024 - 11:00" class="datetime">November 20, 2024</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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=-uwKD0TI 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=-uwKD0TI 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=X1PLTXrA 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=UMAllycL 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=FFALKwIi 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=c6Smt5Zh 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/longstory/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=c6Smt5Zh" width="499" height="294" alt="A spatial map of colon tissue with colored dots showing different cell types." title="A spatial map of colon tissue with colored dots showing different cell types." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Xavier lab </div> <div class="media-caption__description"> A map showing the distribution of different structural cell types in the colon. Fibroblasts are labeled in red, enterocytes in blue, and goblet cells in yellow. </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=/taxonomy/term/1526/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg 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> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/1526/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/1526/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field 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-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The intestine maintains a delicate balance in the body, absorbing nutrients and water while maintaining a healthy relationship with the gut microbiome, but this equilibrium is disrupted in parts of the intestine in conditions such as celiac disease, ulcerative colitis, and Crohn’s disease. Scientists don’t fully understand how different regions of the organ resist or adapt to changes in the environment and how that is disrupted in disease.</p> <p>Now, researchers at the ӳ����ý of MIT and Harvard and Massachusetts General Hospital have analyzed the entire mouse intestine, mapping gene expression and cell states and location in the healthy gut and in response to perturbations such as inflammation. They identified tight regulation of cell types and states in different regions of the organ, as well as a unique segment of the colon that is controlled by immune signals. The findings, which appear today in <em><a href="https://www.nature.com/articles/s41586-024-08216-z" target="_blank">Nature</a></em>, reveal the surprising adaptability and resilience of the intestine to perturbations and highlight the importance of considering how cell processes are regulated and vary across different parts of a tissue or organ.</p> <p>“The intestine and in particular the colon has been studied for decades but it hasn’t been characterized in this way before, and that both forces us to reevaluate many different studies and opens up a window for future research,” said Toufic Mayassi, a co-first author on the study along with Chenhao Li. Mayassi and Li are postdoctoral researchers in the lab of Ramnik Xavier, who is a core institute member at the ӳ����ý, member of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH), and senior author of the study.&nbsp;</p> <p>“This work illustrates that you really have to integrate the spatial relationships governing a given organ into your thinking, and we hope our study provides a platform and framework that helps put both previous and future discoveries in context,” Mayassi said.</p> <p><a href="http://www.broadinstitute.org/node/4721/">Xavier</a> is the director of ӳ����ý’s Immunology Program, as well as the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, director of the Center for Computational and Integrative Biology and member of the Department of Molecular Biology at MGH, and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.</p> <p>“We’ve built a blueprint of the entire gut, and that’s a remarkable achievement,” said Xavier. “We now have a way of studying the whole organ, examining the effect of genetic variants and immune responses associated with diet, the microbiome, and gastrointestinal disease, and designing many other experiments.”</p> <h2>Mapping the intestine</h2> <p>Many previous studies of the gut looked at cells or organ-like assemblies of cells in a dish. While such approaches provide a controlled environment to study the function of specific genetic variants involved in disease, they don’t illustrate how cells from different parts of an intact organ interact to bring about disease.</p> <p>In 2021, Mayassi, who spent his PhD studying immune responses in the intestine, teamed up with Li, a computational biologist, to build a comprehensive map of gene expression across the entire mouse small intestine and colon using spatial transcriptomics and computational approaches.&nbsp;</p> <p>To the researchers’ surprise, the spatial composition of the intestine — the relative location of various cell types and the genes they express — remained relatively stable when certain factors changed. It stayed the same in animals with and without gut microbiota and in tissue collected at night or during the day, suggesting that neither the microbiome nor circadian rhythms impacted the spatial landscape.&nbsp;</p> <p>The intestine also showed signs of resilience. When Mayassi treated the animals with a molecule known to induce inflammation, gene expression and cell spatial distribution changed but showed signs of returning to normal a month later, and had almost entirely recovered by three months. The findings suggest that the gut’s ability to bounce back from changes brought about by inflammation could be critical to intestinal health and function.&nbsp;</p> <p>“As a computational biologist, it is exciting to be involved in generating and exploring such a unique dataset,” Li said. “It opens the door to developing tools for analyzing spatial data and informs the design of future studies on the small and large intestine.”</p> <h2>Immune control</h2> <p>Though the intestine was stable to many influences, unique niches within the organ were affected by the gut microbiota and showed signs of adaptation. Mice that had a normal microbiome expressed unique genes in a specific region of the colon compared to germ-free mice. Using single-cell RNA sequencing, the authors found that the changes occurred in three structural cell types. In particular, goblet cells — cup-shaped cells that secrete mucus — expressed those genes only in the presence of ILC2s, a kind of immune cell.</p> <p>Next, the researchers plan to apply their method to study how other factors including sex, diet, food allergies, and genetic risk factors for conditions such as inflammatory bowel disease impact the intestine’s spatial landscape. They also hope to elucidate the extent to which the findings in mice correlate with spatial control in the human gut.</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 Center for the Study of Inflammatory Bowel Disease, National Institutes of Health, The Leona M. and Harry B. Helmsley Charitable Trust, the Klarman Cell Observatory, the Jill Roberts Institute for Research in IBD, Kenneth Rainin Foundation, the Sanders Family Foundation, Rosanne H. Silbermann Foundation, Linda and Glenn Greenberg, the Allen Discovery Center Program, and Paul G. Allen Frontiers Group advised program of the Paul G. Allen Family Foundation.</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>Mayassi T, Li C, et al. <a href="https://www.nature.com/articles/s41586-024-08216-z" target="_blank">Spatially restricted immune and microbiota-driven adaptation of the gut</a>. <em>Nature</em>. Online November 20, 2024. DOI: 10.1038/s41586-024-08216-z.</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/immunology-program" hreflang="en">Immunology Program</a></div> <div class="field__item"><a href="/broad-tags/xavier-lab" hreflang="en">Xavier Lab</a></div> <div class="field__item"><a href="/broad-tags/spatial-omics-0" hreflang="en">Spatial -omics</a></div> </div> </div> </div> </div> </div> Thu, 03 Sep 2020 15:49:58 +0000 kzusi@broadinstitute.org 647586 at /news/cholesterol-busting-gut-bacteria-may-affect-people%E2%80%99s-cardiac-health <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists find a region of the mouse gut tightly regulated by the immune system</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="2024-11-20T11:00:00-05:00" class="datetime">November 20, 2024</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> <li> <a href="/news">News</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 find a region of the mouse gut tightly regulated by the immune system</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 spatial map of gene expression across the intestine reveals the organ’s remarkable adaptability.</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="2024-11-20T11:00:00-05:00" title="Wednesday, November 20, 2024 - 11:00" class="datetime">November 20, 2024</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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=-uwKD0TI 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=-uwKD0TI 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=X1PLTXrA 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=UMAllycL 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=FFALKwIi 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=c6Smt5Zh 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/longstory/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=c6Smt5Zh" width="499" height="294" alt="A spatial map of colon tissue with colored dots showing different cell types." title="A spatial map of colon tissue with colored dots showing different cell types." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Xavier lab </div> <div class="media-caption__description"> A map showing the distribution of different structural cell types in the colon. Fibroblasts are labeled in red, enterocytes in blue, and goblet cells in yellow. </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=/taxonomy/term/1526/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg 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> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/1526/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/1526/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field 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-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The intestine maintains a delicate balance in the body, absorbing nutrients and water while maintaining a healthy relationship with the gut microbiome, but this equilibrium is disrupted in parts of the intestine in conditions such as celiac disease, ulcerative colitis, and Crohn’s disease. Scientists don’t fully understand how different regions of the organ resist or adapt to changes in the environment and how that is disrupted in disease.</p> <p>Now, researchers at the ӳ����ý of MIT and Harvard and Massachusetts General Hospital have analyzed the entire mouse intestine, mapping gene expression and cell states and location in the healthy gut and in response to perturbations such as inflammation. They identified tight regulation of cell types and states in different regions of the organ, as well as a unique segment of the colon that is controlled by immune signals. The findings, which appear today in <em><a href="https://www.nature.com/articles/s41586-024-08216-z" target="_blank">Nature</a></em>, reveal the surprising adaptability and resilience of the intestine to perturbations and highlight the importance of considering how cell processes are regulated and vary across different parts of a tissue or organ.</p> <p>“The intestine and in particular the colon has been studied for decades but it hasn’t been characterized in this way before, and that both forces us to reevaluate many different studies and opens up a window for future research,” said Toufic Mayassi, a co-first author on the study along with Chenhao Li. Mayassi and Li are postdoctoral researchers in the lab of Ramnik Xavier, who is a core institute member at the ӳ����ý, member of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH), and senior author of the study.&nbsp;</p> <p>“This work illustrates that you really have to integrate the spatial relationships governing a given organ into your thinking, and we hope our study provides a platform and framework that helps put both previous and future discoveries in context,” Mayassi said.</p> <p><a href="http://www.broadinstitute.org/node/4721/">Xavier</a> is the director of ӳ����ý’s Immunology Program, as well as the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, director of the Center for Computational and Integrative Biology and member of the Department of Molecular Biology at MGH, and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.</p> <p>“We’ve built a blueprint of the entire gut, and that’s a remarkable achievement,” said Xavier. “We now have a way of studying the whole organ, examining the effect of genetic variants and immune responses associated with diet, the microbiome, and gastrointestinal disease, and designing many other experiments.”</p> <h2>Mapping the intestine</h2> <p>Many previous studies of the gut looked at cells or organ-like assemblies of cells in a dish. While such approaches provide a controlled environment to study the function of specific genetic variants involved in disease, they don’t illustrate how cells from different parts of an intact organ interact to bring about disease.</p> <p>In 2021, Mayassi, who spent his PhD studying immune responses in the intestine, teamed up with Li, a computational biologist, to build a comprehensive map of gene expression across the entire mouse small intestine and colon using spatial transcriptomics and computational approaches.&nbsp;</p> <p>To the researchers’ surprise, the spatial composition of the intestine — the relative location of various cell types and the genes they express — remained relatively stable when certain factors changed. It stayed the same in animals with and without gut microbiota and in tissue collected at night or during the day, suggesting that neither the microbiome nor circadian rhythms impacted the spatial landscape.&nbsp;</p> <p>The intestine also showed signs of resilience. When Mayassi treated the animals with a molecule known to induce inflammation, gene expression and cell spatial distribution changed but showed signs of returning to normal a month later, and had almost entirely recovered by three months. The findings suggest that the gut’s ability to bounce back from changes brought about by inflammation could be critical to intestinal health and function.&nbsp;</p> <p>“As a computational biologist, it is exciting to be involved in generating and exploring such a unique dataset,” Li said. “It opens the door to developing tools for analyzing spatial data and informs the design of future studies on the small and large intestine.”</p> <h2>Immune control</h2> <p>Though the intestine was stable to many influences, unique niches within the organ were affected by the gut microbiota and showed signs of adaptation. Mice that had a normal microbiome expressed unique genes in a specific region of the colon compared to germ-free mice. Using single-cell RNA sequencing, the authors found that the changes occurred in three structural cell types. In particular, goblet cells — cup-shaped cells that secrete mucus — expressed those genes only in the presence of ILC2s, a kind of immune cell.</p> <p>Next, the researchers plan to apply their method to study how other factors including sex, diet, food allergies, and genetic risk factors for conditions such as inflammatory bowel disease impact the intestine’s spatial landscape. They also hope to elucidate the extent to which the findings in mice correlate with spatial control in the human gut.</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 Center for the Study of Inflammatory Bowel Disease, National Institutes of Health, The Leona M. and Harry B. Helmsley Charitable Trust, the Klarman Cell Observatory, the Jill Roberts Institute for Research in IBD, Kenneth Rainin Foundation, the Sanders Family Foundation, Rosanne H. Silbermann Foundation, Linda and Glenn Greenberg, the Allen Discovery Center Program, and Paul G. Allen Frontiers Group advised program of the Paul G. Allen Family Foundation.</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>Mayassi T, Li C, et al. <a href="https://www.nature.com/articles/s41586-024-08216-z" target="_blank">Spatially restricted immune and microbiota-driven adaptation of the gut</a>. <em>Nature</em>. Online November 20, 2024. DOI: 10.1038/s41586-024-08216-z.</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/immunology-program" hreflang="en">Immunology Program</a></div> <div class="field__item"><a href="/broad-tags/xavier-lab" hreflang="en">Xavier Lab</a></div> <div class="field__item"><a href="/broad-tags/spatial-omics-0" hreflang="en">Spatial -omics</a></div> </div> </div> </div> </div> </div> Mon, 15 Jun 2020 15:42:13 +0000 Corie Lok 630531 at /news/how-immune-system-puts-brakes-allergic-inflammation <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists find a region of the mouse gut tightly regulated by the immune system</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="2024-11-20T11:00:00-05:00" class="datetime">November 20, 2024</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> <li> <a href="/news">News</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 find a region of the mouse gut tightly regulated by the immune system</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 spatial map of gene expression across the intestine reveals the organ’s remarkable adaptability.</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="2024-11-20T11:00:00-05:00" title="Wednesday, November 20, 2024 - 11:00" class="datetime">November 20, 2024</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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=-uwKD0TI 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=-uwKD0TI 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=X1PLTXrA 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=UMAllycL 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=FFALKwIi 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=c6Smt5Zh 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/longstory/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=c6Smt5Zh" width="499" height="294" alt="A spatial map of colon tissue with colored dots showing different cell types." title="A spatial map of colon tissue with colored dots showing different cell types." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Xavier lab </div> <div class="media-caption__description"> A map showing the distribution of different structural cell types in the colon. Fibroblasts are labeled in red, enterocytes in blue, and goblet cells in yellow. </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=/taxonomy/term/1526/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg 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> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/1526/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/1526/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field 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-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The intestine maintains a delicate balance in the body, absorbing nutrients and water while maintaining a healthy relationship with the gut microbiome, but this equilibrium is disrupted in parts of the intestine in conditions such as celiac disease, ulcerative colitis, and Crohn’s disease. Scientists don’t fully understand how different regions of the organ resist or adapt to changes in the environment and how that is disrupted in disease.</p> <p>Now, researchers at the ӳ����ý of MIT and Harvard and Massachusetts General Hospital have analyzed the entire mouse intestine, mapping gene expression and cell states and location in the healthy gut and in response to perturbations such as inflammation. They identified tight regulation of cell types and states in different regions of the organ, as well as a unique segment of the colon that is controlled by immune signals. The findings, which appear today in <em><a href="https://www.nature.com/articles/s41586-024-08216-z" target="_blank">Nature</a></em>, reveal the surprising adaptability and resilience of the intestine to perturbations and highlight the importance of considering how cell processes are regulated and vary across different parts of a tissue or organ.</p> <p>“The intestine and in particular the colon has been studied for decades but it hasn’t been characterized in this way before, and that both forces us to reevaluate many different studies and opens up a window for future research,” said Toufic Mayassi, a co-first author on the study along with Chenhao Li. Mayassi and Li are postdoctoral researchers in the lab of Ramnik Xavier, who is a core institute member at the ӳ����ý, member of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH), and senior author of the study.&nbsp;</p> <p>“This work illustrates that you really have to integrate the spatial relationships governing a given organ into your thinking, and we hope our study provides a platform and framework that helps put both previous and future discoveries in context,” Mayassi said.</p> <p><a href="http://www.broadinstitute.org/node/4721/">Xavier</a> is the director of ӳ����ý’s Immunology Program, as well as the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, director of the Center for Computational and Integrative Biology and member of the Department of Molecular Biology at MGH, and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.</p> <p>“We’ve built a blueprint of the entire gut, and that’s a remarkable achievement,” said Xavier. “We now have a way of studying the whole organ, examining the effect of genetic variants and immune responses associated with diet, the microbiome, and gastrointestinal disease, and designing many other experiments.”</p> <h2>Mapping the intestine</h2> <p>Many previous studies of the gut looked at cells or organ-like assemblies of cells in a dish. While such approaches provide a controlled environment to study the function of specific genetic variants involved in disease, they don’t illustrate how cells from different parts of an intact organ interact to bring about disease.</p> <p>In 2021, Mayassi, who spent his PhD studying immune responses in the intestine, teamed up with Li, a computational biologist, to build a comprehensive map of gene expression across the entire mouse small intestine and colon using spatial transcriptomics and computational approaches.&nbsp;</p> <p>To the researchers’ surprise, the spatial composition of the intestine — the relative location of various cell types and the genes they express — remained relatively stable when certain factors changed. It stayed the same in animals with and without gut microbiota and in tissue collected at night or during the day, suggesting that neither the microbiome nor circadian rhythms impacted the spatial landscape.&nbsp;</p> <p>The intestine also showed signs of resilience. When Mayassi treated the animals with a molecule known to induce inflammation, gene expression and cell spatial distribution changed but showed signs of returning to normal a month later, and had almost entirely recovered by three months. The findings suggest that the gut’s ability to bounce back from changes brought about by inflammation could be critical to intestinal health and function.&nbsp;</p> <p>“As a computational biologist, it is exciting to be involved in generating and exploring such a unique dataset,” Li said. “It opens the door to developing tools for analyzing spatial data and informs the design of future studies on the small and large intestine.”</p> <h2>Immune control</h2> <p>Though the intestine was stable to many influences, unique niches within the organ were affected by the gut microbiota and showed signs of adaptation. Mice that had a normal microbiome expressed unique genes in a specific region of the colon compared to germ-free mice. Using single-cell RNA sequencing, the authors found that the changes occurred in three structural cell types. In particular, goblet cells — cup-shaped cells that secrete mucus — expressed those genes only in the presence of ILC2s, a kind of immune cell.</p> <p>Next, the researchers plan to apply their method to study how other factors including sex, diet, food allergies, and genetic risk factors for conditions such as inflammatory bowel disease impact the intestine’s spatial landscape. They also hope to elucidate the extent to which the findings in mice correlate with spatial control in the human gut.</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 Center for the Study of Inflammatory Bowel Disease, National Institutes of Health, The Leona M. and Harry B. Helmsley Charitable Trust, the Klarman Cell Observatory, the Jill Roberts Institute for Research in IBD, Kenneth Rainin Foundation, the Sanders Family Foundation, Rosanne H. Silbermann Foundation, Linda and Glenn Greenberg, the Allen Discovery Center Program, and Paul G. Allen Frontiers Group advised program of the Paul G. Allen Family Foundation.</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>Mayassi T, Li C, et al. <a href="https://www.nature.com/articles/s41586-024-08216-z" target="_blank">Spatially restricted immune and microbiota-driven adaptation of the gut</a>. <em>Nature</em>. Online November 20, 2024. DOI: 10.1038/s41586-024-08216-z.</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/immunology-program" hreflang="en">Immunology Program</a></div> <div class="field__item"><a href="/broad-tags/xavier-lab" hreflang="en">Xavier Lab</a></div> <div class="field__item"><a href="/broad-tags/spatial-omics-0" hreflang="en">Spatial -omics</a></div> </div> </div> </div> </div> </div> Fri, 22 Nov 2019 15:00:00 +0000 kzusi@broadinstitute.org 625251 at /blog/how-improve-therapies-inflammatory-bowel-disease <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists find a region of the mouse gut tightly regulated by the immune system</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="2024-11-20T11:00:00-05:00" class="datetime">November 20, 2024</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> <li> <a href="/news">News</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 find a region of the mouse gut tightly regulated by the immune system</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 spatial map of gene expression across the intestine reveals the organ’s remarkable adaptability.</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="2024-11-20T11:00:00-05:00" title="Wednesday, November 20, 2024 - 11:00" class="datetime">November 20, 2024</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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=-uwKD0TI 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=-uwKD0TI 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=X1PLTXrA 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=UMAllycL 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=FFALKwIi 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/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=c6Smt5Zh 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/longstory/main_Figure_ӳ����ýWriteup_Nature-01.png?itok=c6Smt5Zh" width="499" height="294" alt="A spatial map of colon tissue with colored dots showing different cell types." title="A spatial map of colon tissue with colored dots showing different cell types." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Xavier lab </div> <div class="media-caption__description"> A map showing the distribution of different structural cell types in the colon. Fibroblasts are labeled in red, enterocytes in blue, and goblet cells in yellow. </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=/taxonomy/term/1526/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg 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> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/1526/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/1526/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field 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-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The intestine maintains a delicate balance in the body, absorbing nutrients and water while maintaining a healthy relationship with the gut microbiome, but this equilibrium is disrupted in parts of the intestine in conditions such as celiac disease, ulcerative colitis, and Crohn’s disease. Scientists don’t fully understand how different regions of the organ resist or adapt to changes in the environment and how that is disrupted in disease.</p> <p>Now, researchers at the ӳ����ý of MIT and Harvard and Massachusetts General Hospital have analyzed the entire mouse intestine, mapping gene expression and cell states and location in the healthy gut and in response to perturbations such as inflammation. They identified tight regulation of cell types and states in different regions of the organ, as well as a unique segment of the colon that is controlled by immune signals. The findings, which appear today in <em><a href="https://www.nature.com/articles/s41586-024-08216-z" target="_blank">Nature</a></em>, reveal the surprising adaptability and resilience of the intestine to perturbations and highlight the importance of considering how cell processes are regulated and vary across different parts of a tissue or organ.</p> <p>“The intestine and in particular the colon has been studied for decades but it hasn’t been characterized in this way before, and that both forces us to reevaluate many different studies and opens up a window for future research,” said Toufic Mayassi, a co-first author on the study along with Chenhao Li. Mayassi and Li are postdoctoral researchers in the lab of Ramnik Xavier, who is a core institute member at the ӳ����ý, member of the Center for Computational and Integrative Biology at Massachusetts General Hospital (MGH), and senior author of the study.&nbsp;</p> <p>“This work illustrates that you really have to integrate the spatial relationships governing a given organ into your thinking, and we hope our study provides a platform and framework that helps put both previous and future discoveries in context,” Mayassi said.</p> <p><a href="http://www.broadinstitute.org/node/4721/">Xavier</a> is the director of ӳ����ý’s Immunology Program, as well as the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, director of the Center for Computational and Integrative Biology and member of the Department of Molecular Biology at MGH, and co-director of the Center for Microbiome Informatics and Therapeutics at MIT.</p> <p>“We’ve built a blueprint of the entire gut, and that’s a remarkable achievement,” said Xavier. “We now have a way of studying the whole organ, examining the effect of genetic variants and immune responses associated with diet, the microbiome, and gastrointestinal disease, and designing many other experiments.”</p> <h2>Mapping the intestine</h2> <p>Many previous studies of the gut looked at cells or organ-like assemblies of cells in a dish. While such approaches provide a controlled environment to study the function of specific genetic variants involved in disease, they don’t illustrate how cells from different parts of an intact organ interact to bring about disease.</p> <p>In 2021, Mayassi, who spent his PhD studying immune responses in the intestine, teamed up with Li, a computational biologist, to build a comprehensive map of gene expression across the entire mouse small intestine and colon using spatial transcriptomics and computational approaches.&nbsp;</p> <p>To the researchers’ surprise, the spatial composition of the intestine — the relative location of various cell types and the genes they express — remained relatively stable when certain factors changed. It stayed the same in animals with and without gut microbiota and in tissue collected at night or during the day, suggesting that neither the microbiome nor circadian rhythms impacted the spatial landscape.&nbsp;</p> <p>The intestine also showed signs of resilience. When Mayassi treated the animals with a molecule known to induce inflammation, gene expression and cell spatial distribution changed but showed signs of returning to normal a month later, and had almost entirely recovered by three months. The findings suggest that the gut’s ability to bounce back from changes brought about by inflammation could be critical to intestinal health and function.&nbsp;</p> <p>“As a computational biologist, it is exciting to be involved in generating and exploring such a unique dataset,” Li said. “It opens the door to developing tools for analyzing spatial data and informs the design of future studies on the small and large intestine.”</p> <h2>Immune control</h2> <p>Though the intestine was stable to many influences, unique niches within the organ were affected by the gut microbiota and showed signs of adaptation. Mice that had a normal microbiome expressed unique genes in a specific region of the colon compared to germ-free mice. Using single-cell RNA sequencing, the authors found that the changes occurred in three structural cell types. In particular, goblet cells — cup-shaped cells that secrete mucus — expressed those genes only in the presence of ILC2s, a kind of immune cell.</p> <p>Next, the researchers plan to apply their method to study how other factors including sex, diet, food allergies, and genetic risk factors for conditions such as inflammatory bowel disease impact the intestine’s spatial landscape. They also hope to elucidate the extent to which the findings in mice correlate with spatial control in the human gut.</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 Center for the Study of Inflammatory Bowel Disease, National Institutes of Health, The Leona M. and Harry B. Helmsley Charitable Trust, the Klarman Cell Observatory, the Jill Roberts Institute for Research in IBD, Kenneth Rainin Foundation, the Sanders Family Foundation, Rosanne H. Silbermann Foundation, Linda and Glenn Greenberg, the Allen Discovery Center Program, and Paul G. Allen Frontiers Group advised program of the Paul G. Allen Family Foundation.</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>Mayassi T, Li C, et al. <a href="https://www.nature.com/articles/s41586-024-08216-z" target="_blank">Spatially restricted immune and microbiota-driven adaptation of the gut</a>. <em>Nature</em>. Online November 20, 2024. DOI: 10.1038/s41586-024-08216-z.</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/immunology-program" hreflang="en">Immunology Program</a></div> <div class="field__item"><a href="/broad-tags/xavier-lab" hreflang="en">Xavier Lab</a></div> <div class="field__item"><a href="/broad-tags/spatial-omics-0" hreflang="en">Spatial -omics</a></div> </div> </div> </div> </div> </div> Mon, 07 Oct 2019 18:02:56 +0000 Karen Blum 622506 at