Your browser doesn't support javascript.
loading
Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis.
Smillie, Christopher S; Biton, Moshe; Ordovas-Montanes, Jose; Sullivan, Keri M; Burgin, Grace; Graham, Daniel B; Herbst, Rebecca H; Rogel, Noga; Slyper, Michal; Waldman, Julia; Sud, Malika; Andrews, Elizabeth; Velonias, Gabriella; Haber, Adam L; Jagadeesh, Karthik; Vickovic, Sanja; Yao, Junmei; Stevens, Christine; Dionne, Danielle; Nguyen, Lan T; Villani, Alexandra-Chloé; Hofree, Matan; Creasey, Elizabeth A; Huang, Hailiang; Rozenblatt-Rosen, Orit; Garber, John J; Khalili, Hamed; Desch, A Nicole; Daly, Mark J; Ananthakrishnan, Ashwin N; Shalek, Alex K; Xavier, Ramnik J; Regev, Aviv.
Afiliação
  • Smillie CS; Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
  • Biton M; Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA; Department of Molecular Biology, MGH, Boston, MA, USA.
  • Ordovas-Montanes J; Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA; Institute for Medical Engineering and Science (IMES), MIT, Cambridge, MA, USA; Department of Chemistry, MIT, Cambridge, MA, USA; Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA; Ragon Institute of MGH, MIT and Har
  • Sullivan KM; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, MGH, Boston, MA, USA.
  • Burgin G; Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
  • Graham DB; Department of Molecular Biology, MGH, Boston, MA, USA; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, MGH, Boston, MA, USA; Broad Institute, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Center for Microbiome Informatics and Therapeutics, MIT, Cambridge,
  • Herbst RH; Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA; Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
  • Rogel N; Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
  • Slyper M; Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
  • Waldman J; Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
  • Sud M; Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
  • Andrews E; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, MGH, Boston, MA, USA.
  • Velonias G; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, MGH, Boston, MA, USA.
  • Haber AL; Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
  • Jagadeesh K; Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
  • Vickovic S; Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
  • Yao J; Center for Computational and Integrative Biology, MGH, Boston, MA, USA.
  • Stevens C; Broad Institute, Cambridge, MA, USA.
  • Dionne D; Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
  • Nguyen LT; Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
  • Villani AC; Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA; Center for Immunology and Inflammatory Diseases, Department of Medicine, MGH, Boston, MA, USA.
  • Hofree M; Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
  • Creasey EA; Center for Computational and Integrative Biology, MGH, Boston, MA, USA.
  • Huang H; Medical and Population Genetics, Broad Institute, Cambridge, MA, USA; Analytical and Translational Genetics Unit, MGH, Boston, MA, USA.
  • Rozenblatt-Rosen O; Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.
  • Garber JJ; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, MGH, Boston, MA, USA.
  • Khalili H; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, MGH, Boston, MA, USA.
  • Desch AN; Broad Institute, Cambridge, MA, USA; Center for Computational and Integrative Biology, MGH, Boston, MA, USA.
  • Daly MJ; Medical and Population Genetics, Broad Institute, Cambridge, MA, USA; Analytical and Translational Genetics Unit, MGH, Boston, MA, USA; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
  • Ananthakrishnan AN; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, MGH, Boston, MA, USA. Electronic address: aananthakrishnan@mgh.harvard.edu.
  • Shalek AK; Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA; Institute for Medical Engineering and Science (IMES), MIT, Cambridge, MA, USA; Department of Chemistry, MIT, Cambridge, MA, USA; Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA; Ragon Institute of MGH, MIT and Har
  • Xavier RJ; Department of Molecular Biology, MGH, Boston, MA, USA; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, MGH, Boston, MA, USA; Broad Institute, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; Center for Microbiome Informatics and Therapeutics, MIT, Cambridge,
  • Regev A; Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA; Howard Hughes Medical Institute and Koch Institute for Integrative Cancer Research, Department of Biology, MIT, Cambridge, MA, USA. Electronic address: aregev@broadinstitute.org.
Cell ; 178(3): 714-730.e22, 2019 07 25.
Article em En | MEDLINE | ID: mdl-31348891
ABSTRACT
Genome-wide association studies (GWAS) have revealed risk alleles for ulcerative colitis (UC). To understand their cell type specificities and pathways of action, we generate an atlas of 366,650 cells from the colon mucosa of 18 UC patients and 12 healthy individuals, revealing 51 epithelial, stromal, and immune cell subsets, including BEST4+ enterocytes, microfold-like cells, and IL13RA2+IL11+ inflammatory fibroblasts, which we associate with resistance to anti-TNF treatment. Inflammatory fibroblasts, inflammatory monocytes, microfold-like cells, and T cells that co-express CD8 and IL-17 expand with disease, forming intercellular interaction hubs. Many UC risk genes are cell type specific and co-regulated within relatively few gene modules, suggesting convergence onto limited sets of cell types and pathways. Using this observation, we nominate and infer functions for specific risk genes across GWAS loci. Our work provides a framework for interrogating complex human diseases and mapping risk variants to cell types and pathways.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colite Ulcerativa / Colo Tipo de estudo: Etiology_studies / Observational_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colite Ulcerativa / Colo Tipo de estudo: Etiology_studies / Observational_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos