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T Helper Cell Cytokines Modulate Intestinal Stem Cell Renewal and Differentiation.
Biton, Moshe; Haber, Adam L; Rogel, Noga; Burgin, Grace; Beyaz, Semir; Schnell, Alexandra; Ashenberg, Orr; Su, Chien-Wen; Smillie, Christopher; Shekhar, Karthik; Chen, Zuojia; Wu, Chuan; Ordovas-Montanes, Jose; Alvarez, David; Herbst, Rebecca H; Zhang, Mei; Tirosh, Itay; Dionne, Danielle; Nguyen, Lan T; Xifaras, Michael E; Shalek, Alex K; von Andrian, Ulrich H; Graham, Daniel B; Rozenblatt-Rosen, Orit; Shi, Hai Ning; Kuchroo, Vijay; Yilmaz, Omer H; Regev, Aviv; Xavier, Ramnik J.
Afiliação
  • Biton M; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Haber AL; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Rogel N; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Burgin G; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Beyaz S; The David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, MA 02139, USA; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell
  • Schnell A; Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Ashenberg O; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Su CW; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
  • Smillie C; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Shekhar K; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Chen Z; Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Wu C; Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Ordovas-Montanes J; Institute for Medical Engineering & Science (IMES) and Department of Chemistry, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; The David H. Ko
  • Alvarez D; Department of Microbiology & Immunobiology and Center for Immune Imaging, Harvard Medical School, Boston, MA 02115, USA.
  • Herbst RH; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02114, USA.
  • Zhang M; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
  • Tirosh I; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
  • Dionne D; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Nguyen LT; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Xifaras ME; The David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, MA 02139, USA.
  • Shalek AK; Institute for Medical Engineering & Science (IMES) and Department of Chemistry, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; The David H. Ko
  • von Andrian UH; Department of Microbiology & Immunobiology and Center for Immune Imaging, Harvard Medical School, Boston, MA 02115, USA.
  • Graham DB; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Rozenblatt-Rosen O; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Shi HN; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
  • Kuchroo V; Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Yilmaz OH; The David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, MA 02139, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Regev A; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; The David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, MIT, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technol
  • Xavier RJ; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Microb
Cell ; 175(5): 1307-1320.e22, 2018 11 15.
Article em En | MEDLINE | ID: mdl-30392957
In the small intestine, a niche of accessory cell types supports the generation of mature epithelial cell types from intestinal stem cells (ISCs). It is unclear, however, if and how immune cells in the niche affect ISC fate or the balance between self-renewal and differentiation. Here, we use single-cell RNA sequencing (scRNA-seq) to identify MHC class II (MHCII) machinery enrichment in two subsets of Lgr5+ ISCs. We show that MHCII+ Lgr5+ ISCs are non-conventional antigen-presenting cells in co-cultures with CD4+ T helper (Th) cells. Stimulation of intestinal organoids with key Th cytokines affects Lgr5+ ISC renewal and differentiation in opposing ways: pro-inflammatory signals promote differentiation, while regulatory cells and cytokines reduce it. In vivo genetic perturbation of Th cells or MHCII expression on Lgr5+ ISCs impacts epithelial cell differentiation and IEC fate during infection. These interactions between Th cells and Lgr5+ ISCs, thus, orchestrate tissue-wide responses to external signals.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células-Tronco / Diferenciação Celular / Interleucina-10 / Linfócitos T Auxiliares-Indutores / Autorrenovação Celular Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células-Tronco / Diferenciação Celular / Interleucina-10 / Linfócitos T Auxiliares-Indutores / Autorrenovação Celular Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Cell Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos