/ en /news/single-cell-analysis-crohns-disease-reveals-detailed-picture-inflammation-gut <span class="field field--name-title field--type-string field--label-hidden"><h1>Single-cell analysis of Crohn’s disease reveals a detailed picture of inflammation in the gut</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="2023-01-30T09:12:04-05:00" class="datetime">January 30, 2023</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 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field--type-created field--label-hidden"><time datetime="2023-01-30T09:12:04-05:00" title="Monday, January 30, 2023 - 09:12" class="datetime">January 30, 2023</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/edited_rnf168.png?h=4252d3b7&amp;itok=kM-ae1aK 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/edited_rnf168.png?h=4252d3b7&amp;itok=kM-ae1aK 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/edited_rnf168.png?h=4252d3b7&amp;itok=IFygcudm 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/edited_rnf168.png?h=4252d3b7&amp;itok=rVkyD9E2 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/edited_rnf168.png?h=4252d3b7&amp;itok=ecUk0CAJ 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/edited_rnf168.png?h=4252d3b7&amp;itok=5PbOft7b 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/edited_rnf168.png?h=4252d3b7&amp;itok=5PbOft7b" width="499" height="294" alt="Collagen (green) and cell nuclei (blue) in fibroblasts with knockdown of the gene RNF168, which affects collagen production." title="Collagen (green) and cell nuclei (blue) in fibroblasts with knockdown of the gene RNF168, which affects collagen production." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Vladislav Pokatayev </div> <div class="media-caption__description"> Fluorescence image of fibroblasts showing cell nuclei (blue) and collagen (green) after knockdown of the gene RNF168 — one of three genes researchers found that are involved in collagen production and likely contribute to scar tissue in the gut. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block 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srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2022/main_Granulomas_in_an_intestinal_lymph_node_in_Crohn_s_disease%2C_HE_3.png?h=d3e04ee7&amp;itok=9XDCgW0R 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/main_Granulomas_in_an_intestinal_lymph_node_in_Crohn_s_disease%2C_HE_3.png?h=d3e04ee7&amp;itok=HSFEfIoK 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <img loading="eager" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/main_Granulomas_in_an_intestinal_lymph_node_in_Crohn_s_disease%2C_HE_3.png?h=d3e04ee7&amp;itok=HSFEfIoK" width="220" height="186" alt="A histological slide showing tissue from an intenstinal lymph node in a patient with Crohn's disease." title="A histological slide showing tissue from an intenstinal lymph node in 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srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=nXpS1VA0 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=KxX33-rZ 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <img loading="eager" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=KxX33-rZ" width="220" height="186" alt="A snapshot of T cells expressing &lt;i&gt;CD4&lt;/i&gt; (green), &lt;i&gt;CD8&lt;/i&gt; (white), and &lt;i&gt;IL-17&lt;/i&gt; (red) in inflamed colon tissue." title="A snapshot of T cells expressing &lt;i&gt;CD4&lt;/i&gt; (green), &lt;i&gt;CD8&lt;/i&gt; (white), and &lt;i&gt;IL-17&lt;/i&gt; (red) in inflamed colon tissue." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/single-cell-atlas-reveals-underlying-building-blocks-ulcerative-colitis" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single-cell atlas reveals underlying building blocks of ulcerative colitis</span> </a> </div> </article> </div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related people</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/bios/ramnik-xavier">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Researchers at the ӳ����ý of MIT and Harvard and Massachusetts General Hospital have constructed a high-resolution cellular map of Crohn’s disease, a chronic condition in which a hyperactive immune system causes inflammation throughout the gut, leading to symptoms including abdominal pain, diarrhea, and weight loss. The disease is difficult to treat and often requires hospitalization.</p> <p>The atlas is the largest study of single cells from Crohn’s patients to date, and contains the gene expression profiles of more than 700,000 cells from 71 healthy individuals and patients in varying states of inflammation.</p> <p>Published today in <a href="https://www.cell.com/immunity/fulltext/S1074-7613(23)00012-2" target="_blank"><em>Immunity</em></a>, the findings offer a detailed cellular portrait into the biological processes underlying Crohn’s that are unique to the small and large intestines. The data also reveal genes and pathways involved in complications of the disease, which could one day be targeted by new drugs. Moreover, the results could help researchers predict and ultimately prevent flares of symptoms, or understand why some patients respond to treatments and others don’t.</p> <p>“We’re beginning to see that Crohn’s disease is not one disease, and that it has many subtypes,” said <a href="/bios/ramnik-xavier">Ramnik Xavier</a>, senior author of the study, core institute member and director of the <a href="/klarman-cell-observatory">Klarman Cell Observatory</a> at the ӳ����ý. Xavier is also the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, director of the Center for Computational and Integrative Biology and core member in the Department of Molecular Biology at Massachusetts General Hospital, and co-director of the Center for Microbiome Informatics and Therapeutics at MIT. Lingjia Kong, a research scientist in Xavier’s lab, was the study’s first author.</p> <p>“We really wanted to build a resource for the field,” said Jacques Deguine, an author on the study and the associate director of the Immunology Program at the ӳ����ý. “There have been atlases across a range of diseases, but now our field has grown enough that we can start tackling these questions in complex diseases, involving different organs. This is moving the needle towards an individualized understanding of biology.”</p> <h2>Inflammation insights</h2> <p>Previous genetic <a href="https://www.nature.com/articles/s41586-020-2025-2" target="_blank">studies</a> have identified more than 200 places in the genome linked to Crohn’s. But Xavier’s team knew that to fully understand the disease, they’d need a cellular map that captured its full complexity. They studied inflamed and non-inflamed cells from both segments of the gastrointestinal tract: the large intestine and the ileum, the last segment of the small intestine that is often affected in Crohn's disease.</p> <p>The scientists used single-cell RNA sequencing to analyze gene activity in the individual gut cells. They found that immune cells and the stroma — the cells inside the gut that shape and support underlying connective tissue — changed in composition during disease. The lining of the intestines showed more changes in gene expression, with some changes unique to the large or small intestine. They also found that expression of genes previously linked to disease risk was distinct in each organ.</p> <p>“I think this really lays the foundation for understanding why Crohn’s disease inflammation manifests in one organ versus another, and how some treatments might influence different disease subtypes differently,” Deguine said.</p> <h2>Towards personalized medicine</h2> <p>About 50 to 60 percent of Crohn’s patients respond to drugs and some experience a relapse of symptoms. Xavier said this suggests that Crohn’s is caused by a variety of biological mechanisms requiring treatments that are tailored to individual patients. He and Deguine added that many of their team’s findings point towards possible targets for personalized treatments. For instance, they identified three genes involved in collagen production that likely contribute to scar tissue in the gut, making the intestines stiffer and less able to pass along food — a common complication of Crohn’s.</p> <p>To their surprise, the researchers discovered that Crohn’s patients had certain gene expression signatures even when their tissues didn’t look inflamed. This could indicate that there are detectable signs of disease even when the tissue appears to be healed on an endoscopy. Understanding the pathways that contribute to low-grade inflammation could help predict when symptoms will flare.</p> <p>In the future, Xavier’s team plans to extend their atlas by collecting samples from patients of a range of ancestries. Deguine also hopes to study patients before and after different treatments to track how their disease progresses.&nbsp;</p> <p>“These projects are collaborative studies that include patients, clinicians, clinical coordinators, data generators, and computational biologists,” said Xavier. “It’s becoming clear that this is how biology needs to be done to have a real impact on human disease.”</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 Helmsley Charitable Trust and the National Institutes of Health.</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(s) cited:</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Kong L et al. <a href="http://www.cell.com/immunity/fulltext/S1074-7613(23)00012-2" target="_blank">The landscape of immune dysregulation in Crohn’s Disease revealed through single-cell transcriptomic profiling in the ileum and colon</a>. <em>Immunity</em>. Online January 30, 2023. DOI:10.1016/j.immuni.2023.01.002.</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/klarman-cell-observatory" hreflang="en">Klarman Cell Observatory</a></div> <div class="field__item"><a href="/broad-tags/inflammatory-bowel-disease" hreflang="en">Inflammatory bowel disease</a></div> <div class="field__item"><a href="/broad-tags/ramnik-xavier" hreflang="en">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> Mon, 30 Jan 2023 14:12:04 +0000 adicorat 1281591 at /news/how-body-identifies-helpful-bacteria <span class="field field--name-title field--type-string field--label-hidden"><h1>Single-cell analysis of Crohn’s disease reveals a detailed picture of inflammation in the gut</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="2023-01-30T09:12:04-05:00" class="datetime">January 30, 2023</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>Single-cell analysis of Crohn’s disease reveals a detailed picture of inflammation in the gut</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"></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="2023-01-30T09:12:04-05:00" title="Monday, January 30, 2023 - 09:12" class="datetime">January 30, 2023</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/edited_rnf168.png?h=4252d3b7&amp;itok=kM-ae1aK 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/edited_rnf168.png?h=4252d3b7&amp;itok=kM-ae1aK 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/edited_rnf168.png?h=4252d3b7&amp;itok=IFygcudm 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/edited_rnf168.png?h=4252d3b7&amp;itok=rVkyD9E2 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/edited_rnf168.png?h=4252d3b7&amp;itok=ecUk0CAJ 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/edited_rnf168.png?h=4252d3b7&amp;itok=5PbOft7b 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/edited_rnf168.png?h=4252d3b7&amp;itok=5PbOft7b" width="499" height="294" alt="Collagen (green) and cell nuclei (blue) in fibroblasts with knockdown of the gene RNF168, which affects collagen production." title="Collagen (green) and cell nuclei (blue) in fibroblasts with knockdown of the gene RNF168, which affects collagen production." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Vladislav Pokatayev </div> <div class="media-caption__description"> Fluorescence image of fibroblasts showing cell nuclei (blue) and collagen (green) after knockdown of the gene RNF168 — one of three genes researchers found that are involved in collagen production and likely contribute to scar tissue in the gut. </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" 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class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related people</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/bios/ramnik-xavier">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Researchers at the ӳ����ý of MIT and Harvard and Massachusetts General Hospital have constructed a high-resolution cellular map of Crohn’s disease, a chronic condition in which a hyperactive immune system causes inflammation throughout the gut, leading to symptoms including abdominal pain, diarrhea, and weight loss. The disease is difficult to treat and often requires hospitalization.</p> <p>The atlas is the largest study of single cells from Crohn’s patients to date, and contains the gene expression profiles of more than 700,000 cells from 71 healthy individuals and patients in varying states of inflammation.</p> <p>Published today in <a href="https://www.cell.com/immunity/fulltext/S1074-7613(23)00012-2" target="_blank"><em>Immunity</em></a>, the findings offer a detailed cellular portrait into the biological processes underlying Crohn’s that are unique to the small and large intestines. The data also reveal genes and pathways involved in complications of the disease, which could one day be targeted by new drugs. Moreover, the results could help researchers predict and ultimately prevent flares of symptoms, or understand why some patients respond to treatments and others don’t.</p> <p>“We’re beginning to see that Crohn’s disease is not one disease, and that it has many subtypes,” said <a href="/bios/ramnik-xavier">Ramnik Xavier</a>, senior author of the study, core institute member and director of the <a href="/klarman-cell-observatory">Klarman Cell Observatory</a> at the ӳ����ý. Xavier is also the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, director of the Center for Computational and Integrative Biology and core member in the Department of Molecular Biology at Massachusetts General Hospital, and co-director of the Center for Microbiome Informatics and Therapeutics at MIT. Lingjia Kong, a research scientist in Xavier’s lab, was the study’s first author.</p> <p>“We really wanted to build a resource for the field,” said Jacques Deguine, an author on the study and the associate director of the Immunology Program at the ӳ����ý. “There have been atlases across a range of diseases, but now our field has grown enough that we can start tackling these questions in complex diseases, involving different organs. This is moving the needle towards an individualized understanding of biology.”</p> <h2>Inflammation insights</h2> <p>Previous genetic <a href="https://www.nature.com/articles/s41586-020-2025-2" target="_blank">studies</a> have identified more than 200 places in the genome linked to Crohn’s. But Xavier’s team knew that to fully understand the disease, they’d need a cellular map that captured its full complexity. They studied inflamed and non-inflamed cells from both segments of the gastrointestinal tract: the large intestine and the ileum, the last segment of the small intestine that is often affected in Crohn's disease.</p> <p>The scientists used single-cell RNA sequencing to analyze gene activity in the individual gut cells. They found that immune cells and the stroma — the cells inside the gut that shape and support underlying connective tissue — changed in composition during disease. The lining of the intestines showed more changes in gene expression, with some changes unique to the large or small intestine. They also found that expression of genes previously linked to disease risk was distinct in each organ.</p> <p>“I think this really lays the foundation for understanding why Crohn’s disease inflammation manifests in one organ versus another, and how some treatments might influence different disease subtypes differently,” Deguine said.</p> <h2>Towards personalized medicine</h2> <p>About 50 to 60 percent of Crohn’s patients respond to drugs and some experience a relapse of symptoms. Xavier said this suggests that Crohn’s is caused by a variety of biological mechanisms requiring treatments that are tailored to individual patients. He and Deguine added that many of their team’s findings point towards possible targets for personalized treatments. For instance, they identified three genes involved in collagen production that likely contribute to scar tissue in the gut, making the intestines stiffer and less able to pass along food — a common complication of Crohn’s.</p> <p>To their surprise, the researchers discovered that Crohn’s patients had certain gene expression signatures even when their tissues didn’t look inflamed. This could indicate that there are detectable signs of disease even when the tissue appears to be healed on an endoscopy. Understanding the pathways that contribute to low-grade inflammation could help predict when symptoms will flare.</p> <p>In the future, Xavier’s team plans to extend their atlas by collecting samples from patients of a range of ancestries. Deguine also hopes to study patients before and after different treatments to track how their disease progresses.&nbsp;</p> <p>“These projects are collaborative studies that include patients, clinicians, clinical coordinators, data generators, and computational biologists,” said Xavier. “It’s becoming clear that this is how biology needs to be done to have a real impact on human disease.”</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 Helmsley Charitable Trust and the National Institutes of Health.</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(s) cited:</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Kong L et al. <a href="http://www.cell.com/immunity/fulltext/S1074-7613(23)00012-2" target="_blank">The landscape of immune dysregulation in Crohn’s Disease revealed through single-cell transcriptomic profiling in the ileum and colon</a>. <em>Immunity</em>. Online January 30, 2023. DOI:10.1016/j.immuni.2023.01.002.</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/klarman-cell-observatory" hreflang="en">Klarman Cell Observatory</a></div> <div class="field__item"><a href="/broad-tags/inflammatory-bowel-disease" hreflang="en">Inflammatory bowel disease</a></div> <div class="field__item"><a href="/broad-tags/ramnik-xavier" hreflang="en">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> Fri, 16 Sep 2022 15:00:00 +0000 aviveros@broadinstitute.org 1192581 at /news/large-sequencing-effort-links-new-genes-crohns-disease-risk <span class="field field--name-title field--type-string field--label-hidden"><h1>Single-cell analysis of Crohn’s disease reveals a detailed picture of inflammation in the gut</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="2023-01-30T09:12:04-05:00" class="datetime">January 30, 2023</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>Single-cell analysis of Crohn’s disease reveals a detailed picture of inflammation in the gut</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"></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="2023-01-30T09:12:04-05:00" title="Monday, January 30, 2023 - 09:12" class="datetime">January 30, 2023</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/edited_rnf168.png?h=4252d3b7&amp;itok=kM-ae1aK 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/edited_rnf168.png?h=4252d3b7&amp;itok=kM-ae1aK 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/edited_rnf168.png?h=4252d3b7&amp;itok=IFygcudm 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/edited_rnf168.png?h=4252d3b7&amp;itok=rVkyD9E2 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/edited_rnf168.png?h=4252d3b7&amp;itok=ecUk0CAJ 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/edited_rnf168.png?h=4252d3b7&amp;itok=5PbOft7b 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/edited_rnf168.png?h=4252d3b7&amp;itok=5PbOft7b" width="499" height="294" alt="Collagen (green) and cell nuclei (blue) in fibroblasts with knockdown of the gene RNF168, which affects collagen production." title="Collagen (green) and cell nuclei (blue) in fibroblasts with knockdown of the gene RNF168, which affects collagen production." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Vladislav Pokatayev </div> <div class="media-caption__description"> Fluorescence image of fibroblasts showing cell nuclei (blue) and collagen (green) after knockdown of the gene RNF168 — one of three genes researchers found that are involved in collagen production and likely contribute to scar tissue in the gut. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block 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srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2022/main_Granulomas_in_an_intestinal_lymph_node_in_Crohn_s_disease%2C_HE_3.png?h=d3e04ee7&amp;itok=9XDCgW0R 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/main_Granulomas_in_an_intestinal_lymph_node_in_Crohn_s_disease%2C_HE_3.png?h=d3e04ee7&amp;itok=HSFEfIoK 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <img loading="eager" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/main_Granulomas_in_an_intestinal_lymph_node_in_Crohn_s_disease%2C_HE_3.png?h=d3e04ee7&amp;itok=HSFEfIoK" width="220" height="186" alt="A histological slide showing tissue from an intenstinal lymph node in a patient with Crohn's disease." title="A histological slide showing tissue from an intenstinal lymph node in a patient with Crohn's disease." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/large-sequencing-effort-links-new-genes-crohns-disease-risk" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Large sequencing effort links new genes to Crohn’s disease risk</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/single-cell-atlas-reveals-underlying-building-blocks-ulcerative-colitis" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/single-cell-atlas-reveals-underlying-building-blocks-ulcerative-colitis"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=tco_KF2a 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=tco_KF2a 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=Kn5qRKpZ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=Kn5qRKpZ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=nXpS1VA0 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=KxX33-rZ 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <img loading="eager" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=KxX33-rZ" width="220" height="186" alt="A snapshot of T cells expressing &lt;i&gt;CD4&lt;/i&gt; (green), &lt;i&gt;CD8&lt;/i&gt; (white), and &lt;i&gt;IL-17&lt;/i&gt; (red) in inflamed colon tissue." title="A snapshot of T cells expressing &lt;i&gt;CD4&lt;/i&gt; (green), &lt;i&gt;CD8&lt;/i&gt; (white), and &lt;i&gt;IL-17&lt;/i&gt; (red) in inflamed colon tissue." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/single-cell-atlas-reveals-underlying-building-blocks-ulcerative-colitis" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single-cell atlas reveals underlying building blocks of ulcerative colitis</span> </a> </div> </article> </div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related people</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/bios/ramnik-xavier">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Researchers at the ӳ����ý of MIT and Harvard and Massachusetts General Hospital have constructed a high-resolution cellular map of Crohn’s disease, a chronic condition in which a hyperactive immune system causes inflammation throughout the gut, leading to symptoms including abdominal pain, diarrhea, and weight loss. The disease is difficult to treat and often requires hospitalization.</p> <p>The atlas is the largest study of single cells from Crohn’s patients to date, and contains the gene expression profiles of more than 700,000 cells from 71 healthy individuals and patients in varying states of inflammation.</p> <p>Published today in <a href="https://www.cell.com/immunity/fulltext/S1074-7613(23)00012-2" target="_blank"><em>Immunity</em></a>, the findings offer a detailed cellular portrait into the biological processes underlying Crohn’s that are unique to the small and large intestines. The data also reveal genes and pathways involved in complications of the disease, which could one day be targeted by new drugs. Moreover, the results could help researchers predict and ultimately prevent flares of symptoms, or understand why some patients respond to treatments and others don’t.</p> <p>“We’re beginning to see that Crohn’s disease is not one disease, and that it has many subtypes,” said <a href="/bios/ramnik-xavier">Ramnik Xavier</a>, senior author of the study, core institute member and director of the <a href="/klarman-cell-observatory">Klarman Cell Observatory</a> at the ӳ����ý. Xavier is also the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, director of the Center for Computational and Integrative Biology and core member in the Department of Molecular Biology at Massachusetts General Hospital, and co-director of the Center for Microbiome Informatics and Therapeutics at MIT. Lingjia Kong, a research scientist in Xavier’s lab, was the study’s first author.</p> <p>“We really wanted to build a resource for the field,” said Jacques Deguine, an author on the study and the associate director of the Immunology Program at the ӳ����ý. “There have been atlases across a range of diseases, but now our field has grown enough that we can start tackling these questions in complex diseases, involving different organs. This is moving the needle towards an individualized understanding of biology.”</p> <h2>Inflammation insights</h2> <p>Previous genetic <a href="https://www.nature.com/articles/s41586-020-2025-2" target="_blank">studies</a> have identified more than 200 places in the genome linked to Crohn’s. But Xavier’s team knew that to fully understand the disease, they’d need a cellular map that captured its full complexity. They studied inflamed and non-inflamed cells from both segments of the gastrointestinal tract: the large intestine and the ileum, the last segment of the small intestine that is often affected in Crohn's disease.</p> <p>The scientists used single-cell RNA sequencing to analyze gene activity in the individual gut cells. They found that immune cells and the stroma — the cells inside the gut that shape and support underlying connective tissue — changed in composition during disease. The lining of the intestines showed more changes in gene expression, with some changes unique to the large or small intestine. They also found that expression of genes previously linked to disease risk was distinct in each organ.</p> <p>“I think this really lays the foundation for understanding why Crohn’s disease inflammation manifests in one organ versus another, and how some treatments might influence different disease subtypes differently,” Deguine said.</p> <h2>Towards personalized medicine</h2> <p>About 50 to 60 percent of Crohn’s patients respond to drugs and some experience a relapse of symptoms. Xavier said this suggests that Crohn’s is caused by a variety of biological mechanisms requiring treatments that are tailored to individual patients. He and Deguine added that many of their team’s findings point towards possible targets for personalized treatments. For instance, they identified three genes involved in collagen production that likely contribute to scar tissue in the gut, making the intestines stiffer and less able to pass along food — a common complication of Crohn’s.</p> <p>To their surprise, the researchers discovered that Crohn’s patients had certain gene expression signatures even when their tissues didn’t look inflamed. This could indicate that there are detectable signs of disease even when the tissue appears to be healed on an endoscopy. Understanding the pathways that contribute to low-grade inflammation could help predict when symptoms will flare.</p> <p>In the future, Xavier’s team plans to extend their atlas by collecting samples from patients of a range of ancestries. Deguine also hopes to study patients before and after different treatments to track how their disease progresses.&nbsp;</p> <p>“These projects are collaborative studies that include patients, clinicians, clinical coordinators, data generators, and computational biologists,” said Xavier. “It’s becoming clear that this is how biology needs to be done to have a real impact on human disease.”</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 Helmsley Charitable Trust and the National Institutes of Health.</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(s) cited:</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Kong L et al. <a href="http://www.cell.com/immunity/fulltext/S1074-7613(23)00012-2" target="_blank">The landscape of immune dysregulation in Crohn’s Disease revealed through single-cell transcriptomic profiling in the ileum and colon</a>. <em>Immunity</em>. Online January 30, 2023. DOI:10.1016/j.immuni.2023.01.002.</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/klarman-cell-observatory" hreflang="en">Klarman Cell Observatory</a></div> <div class="field__item"><a href="/broad-tags/inflammatory-bowel-disease" hreflang="en">Inflammatory bowel disease</a></div> <div class="field__item"><a href="/broad-tags/ramnik-xavier" hreflang="en">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> Mon, 29 Aug 2022 08:50:19 +0000 adicorat 1176506 at /news/single-cell-atlas-nerve-cells-gut-reveals-web-connections <span class="field field--name-title field--type-string field--label-hidden"><h1>Single-cell analysis of Crohn’s disease reveals a detailed picture of inflammation in the gut</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="2023-01-30T09:12:04-05:00" class="datetime">January 30, 2023</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>Single-cell analysis of Crohn’s disease reveals a detailed picture of inflammation in the gut</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"></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="2023-01-30T09:12:04-05:00" title="Monday, January 30, 2023 - 09:12" class="datetime">January 30, 2023</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/edited_rnf168.png?h=4252d3b7&amp;itok=kM-ae1aK 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/edited_rnf168.png?h=4252d3b7&amp;itok=kM-ae1aK 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/edited_rnf168.png?h=4252d3b7&amp;itok=IFygcudm 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/edited_rnf168.png?h=4252d3b7&amp;itok=rVkyD9E2 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/edited_rnf168.png?h=4252d3b7&amp;itok=ecUk0CAJ 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/edited_rnf168.png?h=4252d3b7&amp;itok=5PbOft7b 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/edited_rnf168.png?h=4252d3b7&amp;itok=5PbOft7b" width="499" height="294" alt="Collagen (green) and cell nuclei (blue) in fibroblasts with knockdown of the gene RNF168, which affects collagen production." title="Collagen (green) and cell nuclei (blue) in fibroblasts with knockdown of the gene RNF168, which affects collagen production." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Vladislav Pokatayev </div> <div class="media-caption__description"> Fluorescence image of fibroblasts showing cell nuclei (blue) and collagen (green) after knockdown of the gene RNF168 — one of three genes researchers found that are involved in collagen production and likely contribute to scar tissue in the gut. </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" 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(max-width: 539px)" type="image/png" width="220" height="186"> <img loading="eager" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=KxX33-rZ" width="220" height="186" alt="A snapshot of T cells expressing &lt;i&gt;CD4&lt;/i&gt; (green), &lt;i&gt;CD8&lt;/i&gt; (white), and &lt;i&gt;IL-17&lt;/i&gt; (red) in inflamed colon tissue." title="A snapshot of T cells expressing &lt;i&gt;CD4&lt;/i&gt; (green), &lt;i&gt;CD8&lt;/i&gt; (white), and &lt;i&gt;IL-17&lt;/i&gt; (red) in inflamed colon tissue." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/single-cell-atlas-reveals-underlying-building-blocks-ulcerative-colitis" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single-cell atlas reveals underlying building blocks of ulcerative colitis</span> </a> </div> </article> </div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related people</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/bios/ramnik-xavier">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Researchers at the ӳ����ý of MIT and Harvard and Massachusetts General Hospital have constructed a high-resolution cellular map of Crohn’s disease, a chronic condition in which a hyperactive immune system causes inflammation throughout the gut, leading to symptoms including abdominal pain, diarrhea, and weight loss. The disease is difficult to treat and often requires hospitalization.</p> <p>The atlas is the largest study of single cells from Crohn’s patients to date, and contains the gene expression profiles of more than 700,000 cells from 71 healthy individuals and patients in varying states of inflammation.</p> <p>Published today in <a href="https://www.cell.com/immunity/fulltext/S1074-7613(23)00012-2" target="_blank"><em>Immunity</em></a>, the findings offer a detailed cellular portrait into the biological processes underlying Crohn’s that are unique to the small and large intestines. The data also reveal genes and pathways involved in complications of the disease, which could one day be targeted by new drugs. Moreover, the results could help researchers predict and ultimately prevent flares of symptoms, or understand why some patients respond to treatments and others don’t.</p> <p>“We’re beginning to see that Crohn’s disease is not one disease, and that it has many subtypes,” said <a href="/bios/ramnik-xavier">Ramnik Xavier</a>, senior author of the study, core institute member and director of the <a href="/klarman-cell-observatory">Klarman Cell Observatory</a> at the ӳ����ý. Xavier is also the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, director of the Center for Computational and Integrative Biology and core member in the Department of Molecular Biology at Massachusetts General Hospital, and co-director of the Center for Microbiome Informatics and Therapeutics at MIT. Lingjia Kong, a research scientist in Xavier’s lab, was the study’s first author.</p> <p>“We really wanted to build a resource for the field,” said Jacques Deguine, an author on the study and the associate director of the Immunology Program at the ӳ����ý. “There have been atlases across a range of diseases, but now our field has grown enough that we can start tackling these questions in complex diseases, involving different organs. This is moving the needle towards an individualized understanding of biology.”</p> <h2>Inflammation insights</h2> <p>Previous genetic <a href="https://www.nature.com/articles/s41586-020-2025-2" target="_blank">studies</a> have identified more than 200 places in the genome linked to Crohn’s. But Xavier’s team knew that to fully understand the disease, they’d need a cellular map that captured its full complexity. They studied inflamed and non-inflamed cells from both segments of the gastrointestinal tract: the large intestine and the ileum, the last segment of the small intestine that is often affected in Crohn's disease.</p> <p>The scientists used single-cell RNA sequencing to analyze gene activity in the individual gut cells. They found that immune cells and the stroma — the cells inside the gut that shape and support underlying connective tissue — changed in composition during disease. The lining of the intestines showed more changes in gene expression, with some changes unique to the large or small intestine. They also found that expression of genes previously linked to disease risk was distinct in each organ.</p> <p>“I think this really lays the foundation for understanding why Crohn’s disease inflammation manifests in one organ versus another, and how some treatments might influence different disease subtypes differently,” Deguine said.</p> <h2>Towards personalized medicine</h2> <p>About 50 to 60 percent of Crohn’s patients respond to drugs and some experience a relapse of symptoms. Xavier said this suggests that Crohn’s is caused by a variety of biological mechanisms requiring treatments that are tailored to individual patients. He and Deguine added that many of their team’s findings point towards possible targets for personalized treatments. For instance, they identified three genes involved in collagen production that likely contribute to scar tissue in the gut, making the intestines stiffer and less able to pass along food — a common complication of Crohn’s.</p> <p>To their surprise, the researchers discovered that Crohn’s patients had certain gene expression signatures even when their tissues didn’t look inflamed. This could indicate that there are detectable signs of disease even when the tissue appears to be healed on an endoscopy. Understanding the pathways that contribute to low-grade inflammation could help predict when symptoms will flare.</p> <p>In the future, Xavier’s team plans to extend their atlas by collecting samples from patients of a range of ancestries. Deguine also hopes to study patients before and after different treatments to track how their disease progresses.&nbsp;</p> <p>“These projects are collaborative studies that include patients, clinicians, clinical coordinators, data generators, and computational biologists,” said Xavier. “It’s becoming clear that this is how biology needs to be done to have a real impact on human disease.”</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 Helmsley Charitable Trust and the National Institutes of Health.</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(s) cited:</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Kong L et al. <a href="http://www.cell.com/immunity/fulltext/S1074-7613(23)00012-2" target="_blank">The landscape of immune dysregulation in Crohn’s Disease revealed through single-cell transcriptomic profiling in the ileum and colon</a>. <em>Immunity</em>. Online January 30, 2023. DOI:10.1016/j.immuni.2023.01.002.</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/klarman-cell-observatory" hreflang="en">Klarman Cell Observatory</a></div> <div class="field__item"><a href="/broad-tags/inflammatory-bowel-disease" hreflang="en">Inflammatory bowel disease</a></div> <div class="field__item"><a href="/broad-tags/ramnik-xavier" hreflang="en">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> Thu, 03 Sep 2020 15:49:58 +0000 kzusi@broadinstitute.org 647586 at /illuminating-human-biology/inflammatory-bowel-disease <span class="field field--name-title field--type-string field--label-hidden"><h1>Single-cell analysis of Crohn’s disease reveals a detailed picture of inflammation in the gut</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="2023-01-30T09:12:04-05:00" class="datetime">January 30, 2023</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>Single-cell analysis of Crohn’s disease reveals a detailed picture of inflammation in the gut</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"></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="2023-01-30T09:12:04-05:00" title="Monday, January 30, 2023 - 09:12" class="datetime">January 30, 2023</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/edited_rnf168.png?h=4252d3b7&amp;itok=kM-ae1aK 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/edited_rnf168.png?h=4252d3b7&amp;itok=kM-ae1aK 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/edited_rnf168.png?h=4252d3b7&amp;itok=IFygcudm 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/edited_rnf168.png?h=4252d3b7&amp;itok=rVkyD9E2 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/edited_rnf168.png?h=4252d3b7&amp;itok=ecUk0CAJ 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/edited_rnf168.png?h=4252d3b7&amp;itok=5PbOft7b 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/edited_rnf168.png?h=4252d3b7&amp;itok=5PbOft7b" width="499" height="294" alt="Collagen (green) and cell nuclei (blue) in fibroblasts with knockdown of the gene RNF168, which affects collagen production." title="Collagen (green) and cell nuclei (blue) in fibroblasts with knockdown of the gene RNF168, which affects collagen production." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Vladislav Pokatayev </div> <div class="media-caption__description"> Fluorescence image of fibroblasts showing cell nuclei (blue) and collagen (green) after knockdown of the gene RNF168 — one of three genes researchers found that are involved in collagen production and likely contribute to scar tissue in the gut. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block 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srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2022/main_Granulomas_in_an_intestinal_lymph_node_in_Crohn_s_disease%2C_HE_3.png?h=d3e04ee7&amp;itok=9XDCgW0R 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/main_Granulomas_in_an_intestinal_lymph_node_in_Crohn_s_disease%2C_HE_3.png?h=d3e04ee7&amp;itok=HSFEfIoK 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <img loading="eager" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/main_Granulomas_in_an_intestinal_lymph_node_in_Crohn_s_disease%2C_HE_3.png?h=d3e04ee7&amp;itok=HSFEfIoK" width="220" height="186" alt="A histological slide showing tissue from an intenstinal lymph node in a patient with Crohn's disease." title="A histological slide showing tissue from an intenstinal lymph node in a patient with Crohn's disease." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/large-sequencing-effort-links-new-genes-crohns-disease-risk" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Large sequencing effort links new genes to Crohn’s disease risk</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/single-cell-atlas-reveals-underlying-building-blocks-ulcerative-colitis" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/single-cell-atlas-reveals-underlying-building-blocks-ulcerative-colitis"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=tco_KF2a 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=tco_KF2a 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=Kn5qRKpZ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=Kn5qRKpZ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=nXpS1VA0 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=KxX33-rZ 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <img loading="eager" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=KxX33-rZ" width="220" height="186" alt="A snapshot of T cells expressing &lt;i&gt;CD4&lt;/i&gt; (green), &lt;i&gt;CD8&lt;/i&gt; (white), and &lt;i&gt;IL-17&lt;/i&gt; (red) in inflamed colon tissue." title="A snapshot of T cells expressing &lt;i&gt;CD4&lt;/i&gt; (green), &lt;i&gt;CD8&lt;/i&gt; (white), and &lt;i&gt;IL-17&lt;/i&gt; (red) in inflamed colon tissue." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/single-cell-atlas-reveals-underlying-building-blocks-ulcerative-colitis" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single-cell atlas reveals underlying building blocks of ulcerative colitis</span> </a> </div> </article> </div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related people</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/bios/ramnik-xavier">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Researchers at the ӳ����ý of MIT and Harvard and Massachusetts General Hospital have constructed a high-resolution cellular map of Crohn’s disease, a chronic condition in which a hyperactive immune system causes inflammation throughout the gut, leading to symptoms including abdominal pain, diarrhea, and weight loss. The disease is difficult to treat and often requires hospitalization.</p> <p>The atlas is the largest study of single cells from Crohn’s patients to date, and contains the gene expression profiles of more than 700,000 cells from 71 healthy individuals and patients in varying states of inflammation.</p> <p>Published today in <a href="https://www.cell.com/immunity/fulltext/S1074-7613(23)00012-2" target="_blank"><em>Immunity</em></a>, the findings offer a detailed cellular portrait into the biological processes underlying Crohn’s that are unique to the small and large intestines. The data also reveal genes and pathways involved in complications of the disease, which could one day be targeted by new drugs. Moreover, the results could help researchers predict and ultimately prevent flares of symptoms, or understand why some patients respond to treatments and others don’t.</p> <p>“We’re beginning to see that Crohn’s disease is not one disease, and that it has many subtypes,” said <a href="/bios/ramnik-xavier">Ramnik Xavier</a>, senior author of the study, core institute member and director of the <a href="/klarman-cell-observatory">Klarman Cell Observatory</a> at the ӳ����ý. Xavier is also the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, director of the Center for Computational and Integrative Biology and core member in the Department of Molecular Biology at Massachusetts General Hospital, and co-director of the Center for Microbiome Informatics and Therapeutics at MIT. Lingjia Kong, a research scientist in Xavier’s lab, was the study’s first author.</p> <p>“We really wanted to build a resource for the field,” said Jacques Deguine, an author on the study and the associate director of the Immunology Program at the ӳ����ý. “There have been atlases across a range of diseases, but now our field has grown enough that we can start tackling these questions in complex diseases, involving different organs. This is moving the needle towards an individualized understanding of biology.”</p> <h2>Inflammation insights</h2> <p>Previous genetic <a href="https://www.nature.com/articles/s41586-020-2025-2" target="_blank">studies</a> have identified more than 200 places in the genome linked to Crohn’s. But Xavier’s team knew that to fully understand the disease, they’d need a cellular map that captured its full complexity. They studied inflamed and non-inflamed cells from both segments of the gastrointestinal tract: the large intestine and the ileum, the last segment of the small intestine that is often affected in Crohn's disease.</p> <p>The scientists used single-cell RNA sequencing to analyze gene activity in the individual gut cells. They found that immune cells and the stroma — the cells inside the gut that shape and support underlying connective tissue — changed in composition during disease. The lining of the intestines showed more changes in gene expression, with some changes unique to the large or small intestine. They also found that expression of genes previously linked to disease risk was distinct in each organ.</p> <p>“I think this really lays the foundation for understanding why Crohn’s disease inflammation manifests in one organ versus another, and how some treatments might influence different disease subtypes differently,” Deguine said.</p> <h2>Towards personalized medicine</h2> <p>About 50 to 60 percent of Crohn’s patients respond to drugs and some experience a relapse of symptoms. Xavier said this suggests that Crohn’s is caused by a variety of biological mechanisms requiring treatments that are tailored to individual patients. He and Deguine added that many of their team’s findings point towards possible targets for personalized treatments. For instance, they identified three genes involved in collagen production that likely contribute to scar tissue in the gut, making the intestines stiffer and less able to pass along food — a common complication of Crohn’s.</p> <p>To their surprise, the researchers discovered that Crohn’s patients had certain gene expression signatures even when their tissues didn’t look inflamed. This could indicate that there are detectable signs of disease even when the tissue appears to be healed on an endoscopy. Understanding the pathways that contribute to low-grade inflammation could help predict when symptoms will flare.</p> <p>In the future, Xavier’s team plans to extend their atlas by collecting samples from patients of a range of ancestries. Deguine also hopes to study patients before and after different treatments to track how their disease progresses.&nbsp;</p> <p>“These projects are collaborative studies that include patients, clinicians, clinical coordinators, data generators, and computational biologists,” said Xavier. “It’s becoming clear that this is how biology needs to be done to have a real impact on human disease.”</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 Helmsley Charitable Trust and the National Institutes of Health.</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(s) cited:</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Kong L et al. <a href="http://www.cell.com/immunity/fulltext/S1074-7613(23)00012-2" target="_blank">The landscape of immune dysregulation in Crohn’s Disease revealed through single-cell transcriptomic profiling in the ileum and colon</a>. <em>Immunity</em>. Online January 30, 2023. DOI:10.1016/j.immuni.2023.01.002.</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/klarman-cell-observatory" hreflang="en">Klarman Cell Observatory</a></div> <div class="field__item"><a href="/broad-tags/inflammatory-bowel-disease" hreflang="en">Inflammatory bowel disease</a></div> <div class="field__item"><a href="/broad-tags/ramnik-xavier" hreflang="en">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> Tue, 17 Sep 2019 15:34:33 +0000 mnemchuk@broadinstitute.org 610881 at /news/study-reveals-microbes-molecular-role-crohns-disease <span class="field field--name-title field--type-string field--label-hidden"><h1>Single-cell analysis of Crohn’s disease reveals a detailed picture of inflammation in the gut</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="2023-01-30T09:12:04-05:00" class="datetime">January 30, 2023</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>Single-cell analysis of Crohn’s disease reveals a detailed picture of inflammation in the gut</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"></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="2023-01-30T09:12:04-05:00" title="Monday, January 30, 2023 - 09:12" class="datetime">January 30, 2023</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/edited_rnf168.png?h=4252d3b7&amp;itok=kM-ae1aK 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/edited_rnf168.png?h=4252d3b7&amp;itok=kM-ae1aK 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/edited_rnf168.png?h=4252d3b7&amp;itok=IFygcudm 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/edited_rnf168.png?h=4252d3b7&amp;itok=rVkyD9E2 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/edited_rnf168.png?h=4252d3b7&amp;itok=ecUk0CAJ 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/edited_rnf168.png?h=4252d3b7&amp;itok=5PbOft7b 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/edited_rnf168.png?h=4252d3b7&amp;itok=5PbOft7b" width="499" height="294" alt="Collagen (green) and cell nuclei (blue) in fibroblasts with knockdown of the gene RNF168, which affects collagen production." title="Collagen (green) and cell nuclei (blue) in fibroblasts with knockdown of the gene RNF168, which affects collagen production." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Vladislav Pokatayev </div> <div class="media-caption__description"> Fluorescence image of fibroblasts showing cell nuclei (blue) and collagen (green) after knockdown of the gene RNF168 — one of three genes researchers found that are involved in collagen production and likely contribute to scar tissue in the gut. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block 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a patient with Crohn's disease." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/large-sequencing-effort-links-new-genes-crohns-disease-risk" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Large sequencing effort links new genes to Crohn’s disease risk</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/single-cell-atlas-reveals-underlying-building-blocks-ulcerative-colitis" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/single-cell-atlas-reveals-underlying-building-blocks-ulcerative-colitis"><picture> <source 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srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=nXpS1VA0 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=KxX33-rZ 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <img loading="eager" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=KxX33-rZ" width="220" height="186" alt="A snapshot of T cells expressing &lt;i&gt;CD4&lt;/i&gt; (green), &lt;i&gt;CD8&lt;/i&gt; (white), and &lt;i&gt;IL-17&lt;/i&gt; (red) in inflamed colon tissue." title="A snapshot of T cells expressing &lt;i&gt;CD4&lt;/i&gt; (green), &lt;i&gt;CD8&lt;/i&gt; (white), and &lt;i&gt;IL-17&lt;/i&gt; (red) in inflamed colon tissue." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/single-cell-atlas-reveals-underlying-building-blocks-ulcerative-colitis" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single-cell atlas reveals underlying building blocks of ulcerative colitis</span> </a> </div> </article> </div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related people</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/bios/ramnik-xavier">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Researchers at the ӳ����ý of MIT and Harvard and Massachusetts General Hospital have constructed a high-resolution cellular map of Crohn’s disease, a chronic condition in which a hyperactive immune system causes inflammation throughout the gut, leading to symptoms including abdominal pain, diarrhea, and weight loss. The disease is difficult to treat and often requires hospitalization.</p> <p>The atlas is the largest study of single cells from Crohn’s patients to date, and contains the gene expression profiles of more than 700,000 cells from 71 healthy individuals and patients in varying states of inflammation.</p> <p>Published today in <a href="https://www.cell.com/immunity/fulltext/S1074-7613(23)00012-2" target="_blank"><em>Immunity</em></a>, the findings offer a detailed cellular portrait into the biological processes underlying Crohn’s that are unique to the small and large intestines. The data also reveal genes and pathways involved in complications of the disease, which could one day be targeted by new drugs. Moreover, the results could help researchers predict and ultimately prevent flares of symptoms, or understand why some patients respond to treatments and others don’t.</p> <p>“We’re beginning to see that Crohn’s disease is not one disease, and that it has many subtypes,” said <a href="/bios/ramnik-xavier">Ramnik Xavier</a>, senior author of the study, core institute member and director of the <a href="/klarman-cell-observatory">Klarman Cell Observatory</a> at the ӳ����ý. Xavier is also the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, director of the Center for Computational and Integrative Biology and core member in the Department of Molecular Biology at Massachusetts General Hospital, and co-director of the Center for Microbiome Informatics and Therapeutics at MIT. Lingjia Kong, a research scientist in Xavier’s lab, was the study’s first author.</p> <p>“We really wanted to build a resource for the field,” said Jacques Deguine, an author on the study and the associate director of the Immunology Program at the ӳ����ý. “There have been atlases across a range of diseases, but now our field has grown enough that we can start tackling these questions in complex diseases, involving different organs. This is moving the needle towards an individualized understanding of biology.”</p> <h2>Inflammation insights</h2> <p>Previous genetic <a href="https://www.nature.com/articles/s41586-020-2025-2" target="_blank">studies</a> have identified more than 200 places in the genome linked to Crohn’s. But Xavier’s team knew that to fully understand the disease, they’d need a cellular map that captured its full complexity. They studied inflamed and non-inflamed cells from both segments of the gastrointestinal tract: the large intestine and the ileum, the last segment of the small intestine that is often affected in Crohn's disease.</p> <p>The scientists used single-cell RNA sequencing to analyze gene activity in the individual gut cells. They found that immune cells and the stroma — the cells inside the gut that shape and support underlying connective tissue — changed in composition during disease. The lining of the intestines showed more changes in gene expression, with some changes unique to the large or small intestine. They also found that expression of genes previously linked to disease risk was distinct in each organ.</p> <p>“I think this really lays the foundation for understanding why Crohn’s disease inflammation manifests in one organ versus another, and how some treatments might influence different disease subtypes differently,” Deguine said.</p> <h2>Towards personalized medicine</h2> <p>About 50 to 60 percent of Crohn’s patients respond to drugs and some experience a relapse of symptoms. Xavier said this suggests that Crohn’s is caused by a variety of biological mechanisms requiring treatments that are tailored to individual patients. He and Deguine added that many of their team’s findings point towards possible targets for personalized treatments. For instance, they identified three genes involved in collagen production that likely contribute to scar tissue in the gut, making the intestines stiffer and less able to pass along food — a common complication of Crohn’s.</p> <p>To their surprise, the researchers discovered that Crohn’s patients had certain gene expression signatures even when their tissues didn’t look inflamed. This could indicate that there are detectable signs of disease even when the tissue appears to be healed on an endoscopy. Understanding the pathways that contribute to low-grade inflammation could help predict when symptoms will flare.</p> <p>In the future, Xavier’s team plans to extend their atlas by collecting samples from patients of a range of ancestries. Deguine also hopes to study patients before and after different treatments to track how their disease progresses.&nbsp;</p> <p>“These projects are collaborative studies that include patients, clinicians, clinical coordinators, data generators, and computational biologists,” said Xavier. “It’s becoming clear that this is how biology needs to be done to have a real impact on human disease.”</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 Helmsley Charitable Trust and the National Institutes of Health.</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(s) cited:</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Kong L et al. <a href="http://www.cell.com/immunity/fulltext/S1074-7613(23)00012-2" target="_blank">The landscape of immune dysregulation in Crohn’s Disease revealed through single-cell transcriptomic profiling in the ileum and colon</a>. <em>Immunity</em>. Online January 30, 2023. DOI:10.1016/j.immuni.2023.01.002.</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/klarman-cell-observatory" hreflang="en">Klarman Cell Observatory</a></div> <div class="field__item"><a href="/broad-tags/inflammatory-bowel-disease" hreflang="en">Inflammatory bowel disease</a></div> <div class="field__item"><a href="/broad-tags/ramnik-xavier" hreflang="en">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> Mon, 10 Jun 2019 19:10:43 +0000 tulrich@broadinstitute.org 542971 at /news/human-microbiome-project-reveals-how-microbiome-disrupted-during-inflammatory-bowel-disease <span class="field field--name-title field--type-string field--label-hidden"><h1>Single-cell analysis of Crohn’s disease reveals a detailed picture of inflammation in the gut</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="2023-01-30T09:12:04-05:00" class="datetime">January 30, 2023</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>Single-cell analysis of Crohn’s disease reveals a detailed picture of inflammation in the gut</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"></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="2023-01-30T09:12:04-05:00" title="Monday, January 30, 2023 - 09:12" class="datetime">January 30, 2023</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/edited_rnf168.png?h=4252d3b7&amp;itok=kM-ae1aK 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/edited_rnf168.png?h=4252d3b7&amp;itok=kM-ae1aK 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/edited_rnf168.png?h=4252d3b7&amp;itok=IFygcudm 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/edited_rnf168.png?h=4252d3b7&amp;itok=rVkyD9E2 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/edited_rnf168.png?h=4252d3b7&amp;itok=ecUk0CAJ 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/edited_rnf168.png?h=4252d3b7&amp;itok=5PbOft7b 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/edited_rnf168.png?h=4252d3b7&amp;itok=5PbOft7b" width="499" height="294" alt="Collagen (green) and cell nuclei (blue) in fibroblasts with knockdown of the gene RNF168, which affects collagen production." title="Collagen (green) and cell nuclei (blue) in fibroblasts with knockdown of the gene RNF168, which affects collagen production." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Vladislav Pokatayev </div> <div class="media-caption__description"> Fluorescence image of fibroblasts showing cell nuclei (blue) and collagen (green) after knockdown of the gene RNF168 — one of three genes researchers found that are involved in collagen production and likely contribute to scar tissue in the gut. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block 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a patient with Crohn's disease." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/large-sequencing-effort-links-new-genes-crohns-disease-risk" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Large sequencing effort links new genes to Crohn’s disease risk</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/single-cell-atlas-reveals-underlying-building-blocks-ulcerative-colitis" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/single-cell-atlas-reveals-underlying-building-blocks-ulcerative-colitis"><picture> <source 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srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=nXpS1VA0 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=KxX33-rZ 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <img loading="eager" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/UC_cover.png?h=827069f2&amp;itok=KxX33-rZ" width="220" height="186" alt="A snapshot of T cells expressing &lt;i&gt;CD4&lt;/i&gt; (green), &lt;i&gt;CD8&lt;/i&gt; (white), and &lt;i&gt;IL-17&lt;/i&gt; (red) in inflamed colon tissue." title="A snapshot of T cells expressing &lt;i&gt;CD4&lt;/i&gt; (green), &lt;i&gt;CD8&lt;/i&gt; (white), and &lt;i&gt;IL-17&lt;/i&gt; (red) in inflamed colon tissue." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/single-cell-atlas-reveals-underlying-building-blocks-ulcerative-colitis" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single-cell atlas reveals underlying building blocks of ulcerative colitis</span> </a> </div> </article> </div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related people</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/bios/ramnik-xavier">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Researchers at the ӳ����ý of MIT and Harvard and Massachusetts General Hospital have constructed a high-resolution cellular map of Crohn’s disease, a chronic condition in which a hyperactive immune system causes inflammation throughout the gut, leading to symptoms including abdominal pain, diarrhea, and weight loss. The disease is difficult to treat and often requires hospitalization.</p> <p>The atlas is the largest study of single cells from Crohn’s patients to date, and contains the gene expression profiles of more than 700,000 cells from 71 healthy individuals and patients in varying states of inflammation.</p> <p>Published today in <a href="https://www.cell.com/immunity/fulltext/S1074-7613(23)00012-2" target="_blank"><em>Immunity</em></a>, the findings offer a detailed cellular portrait into the biological processes underlying Crohn’s that are unique to the small and large intestines. The data also reveal genes and pathways involved in complications of the disease, which could one day be targeted by new drugs. Moreover, the results could help researchers predict and ultimately prevent flares of symptoms, or understand why some patients respond to treatments and others don’t.</p> <p>“We’re beginning to see that Crohn’s disease is not one disease, and that it has many subtypes,” said <a href="/bios/ramnik-xavier">Ramnik Xavier</a>, senior author of the study, core institute member and director of the <a href="/klarman-cell-observatory">Klarman Cell Observatory</a> at the ӳ����ý. Xavier is also the Kurt J. Isselbacher Professor of Medicine at Harvard Medical School, director of the Center for Computational and Integrative Biology and core member in the Department of Molecular Biology at Massachusetts General Hospital, and co-director of the Center for Microbiome Informatics and Therapeutics at MIT. Lingjia Kong, a research scientist in Xavier’s lab, was the study’s first author.</p> <p>“We really wanted to build a resource for the field,” said Jacques Deguine, an author on the study and the associate director of the Immunology Program at the ӳ����ý. “There have been atlases across a range of diseases, but now our field has grown enough that we can start tackling these questions in complex diseases, involving different organs. This is moving the needle towards an individualized understanding of biology.”</p> <h2>Inflammation insights</h2> <p>Previous genetic <a href="https://www.nature.com/articles/s41586-020-2025-2" target="_blank">studies</a> have identified more than 200 places in the genome linked to Crohn’s. But Xavier’s team knew that to fully understand the disease, they’d need a cellular map that captured its full complexity. They studied inflamed and non-inflamed cells from both segments of the gastrointestinal tract: the large intestine and the ileum, the last segment of the small intestine that is often affected in Crohn's disease.</p> <p>The scientists used single-cell RNA sequencing to analyze gene activity in the individual gut cells. They found that immune cells and the stroma — the cells inside the gut that shape and support underlying connective tissue — changed in composition during disease. The lining of the intestines showed more changes in gene expression, with some changes unique to the large or small intestine. They also found that expression of genes previously linked to disease risk was distinct in each organ.</p> <p>“I think this really lays the foundation for understanding why Crohn’s disease inflammation manifests in one organ versus another, and how some treatments might influence different disease subtypes differently,” Deguine said.</p> <h2>Towards personalized medicine</h2> <p>About 50 to 60 percent of Crohn’s patients respond to drugs and some experience a relapse of symptoms. Xavier said this suggests that Crohn’s is caused by a variety of biological mechanisms requiring treatments that are tailored to individual patients. He and Deguine added that many of their team’s findings point towards possible targets for personalized treatments. For instance, they identified three genes involved in collagen production that likely contribute to scar tissue in the gut, making the intestines stiffer and less able to pass along food — a common complication of Crohn’s.</p> <p>To their surprise, the researchers discovered that Crohn’s patients had certain gene expression signatures even when their tissues didn’t look inflamed. This could indicate that there are detectable signs of disease even when the tissue appears to be healed on an endoscopy. Understanding the pathways that contribute to low-grade inflammation could help predict when symptoms will flare.</p> <p>In the future, Xavier’s team plans to extend their atlas by collecting samples from patients of a range of ancestries. Deguine also hopes to study patients before and after different treatments to track how their disease progresses.&nbsp;</p> <p>“These projects are collaborative studies that include patients, clinicians, clinical coordinators, data generators, and computational biologists,” said Xavier. “It’s becoming clear that this is how biology needs to be done to have a real impact on human disease.”</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 Helmsley Charitable Trust and the National Institutes of Health.</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(s) cited:</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Kong L et al. <a href="http://www.cell.com/immunity/fulltext/S1074-7613(23)00012-2" target="_blank">The landscape of immune dysregulation in Crohn’s Disease revealed through single-cell transcriptomic profiling in the ileum and colon</a>. <em>Immunity</em>. Online January 30, 2023. DOI:10.1016/j.immuni.2023.01.002.</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/klarman-cell-observatory" hreflang="en">Klarman Cell Observatory</a></div> <div class="field__item"><a href="/broad-tags/inflammatory-bowel-disease" hreflang="en">Inflammatory bowel disease</a></div> <div class="field__item"><a href="/broad-tags/ramnik-xavier" hreflang="en">Ramnik Xavier</a></div> </div> </div> </div> </div> </div> Wed, 29 May 2019 15:36:26 +0000 David Cameron 534516 at