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SATB2 preserves colon stem cell identity and mediates ileum-colon conversion via enhancer remodeling.
Gu, Wei; Wang, Hua; Huang, Xiaofeng; Kraiczy, Judith; Singh, Pratik N P; Ng, Charles; Dagdeviren, Sezin; Houghton, Sean; Pellon-Cardenas, Oscar; Lan, Ying; Nie, Yaohui; Zhang, Jiaoyue; Banerjee, Kushal K; Onufer, Emily J; Warner, Brad W; Spence, Jason; Scherl, Ellen; Rafii, Shahin; Lee, Richard T; Verzi, Michael P; Redmond, David; Longman, Randy; Helin, Kristian; Shivdasani, Ramesh A; Zhou, Qiao.
Afiliação
  • Gu W; Division of Regenerative Medicine & Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Wang H; Cell Biology Program and Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, 430 E 67th Street, New York, NY 10065, USA.
  • Huang X; Division of Regenerative Medicine & Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Kraiczy J; Department of Medical Oncology, Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
  • Singh PNP; Department of Medical Oncology, Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
  • Ng C; Jill Roberts Center for Inflammatory Bowel Disease, Weill Cornell Medicine, 1283 York Avenue, New York, NY 10065, USA.
  • Dagdeviren S; Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.
  • Houghton S; Division of Regenerative Medicine & Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Pellon-Cardenas O; Department of Genetics, Rutgers University, 145 Bevier Road, Piscataway, NJ 08854, USA.
  • Lan Y; Division of Regenerative Medicine & Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Nie Y; Division of Regenerative Medicine & Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Zhang J; Division of Regenerative Medicine & Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Banerjee KK; Department of Medical Oncology, Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
  • Onufer EJ; Division of Pediatric Surgery, Department of Surgery, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
  • Warner BW; Division of Pediatric Surgery, Department of Surgery, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
  • Spence J; Department of Internal Medicine, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA.
  • Scherl E; Jill Roberts Center for Inflammatory Bowel Disease, Weill Cornell Medicine, 1283 York Avenue, New York, NY 10065, USA.
  • Rafii S; Division of Regenerative Medicine & Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Lee RT; Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.
  • Verzi MP; Department of Genetics, Rutgers University, 145 Bevier Road, Piscataway, NJ 08854, USA.
  • Redmond D; Division of Regenerative Medicine & Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Longman R; Jill Roberts Center for Inflammatory Bowel Disease, Weill Cornell Medicine, 1283 York Avenue, New York, NY 10065, USA.
  • Helin K; Cell Biology Program and Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, 430 E 67th Street, New York, NY 10065, USA; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen N 2200, Denmark; The Novo Nordisk Foundation for Stem Cell Biology (Danste
  • Shivdasani RA; Department of Medical Oncology, Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
  • Zhou Q; Division of Regenerative Medicine & Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA. Electronic address: jqz4001@med.cornell.edu.
Cell Stem Cell ; 29(1): 101-115.e10, 2022 01 06.
Article em En | MEDLINE | ID: mdl-34582804
ABSTRACT
Adult stem cells maintain regenerative tissue structure and function by producing tissue-specific progeny, but the factors that preserve their tissue identities are not well understood. The small and large intestines differ markedly in cell composition and function, reflecting their distinct stem cell populations. Here we show that SATB2, a colon-restricted chromatin factor, singularly preserves LGR5+ adult colonic stem cell and epithelial identity in mice and humans. Satb2 loss in adult mice leads to stable conversion of colonic stem cells into small intestine ileal-like stem cells and replacement of the colonic mucosa with one that resembles the ileum. Conversely, SATB2 confers colonic properties on the mouse ileum. Human colonic organoids also adopt ileal characteristics upon SATB2 loss. SATB2 regulates colonic identity in part by modulating enhancer binding of the intestinal transcription factors CDX2 and HNF4A. Our study uncovers a conserved core regulator of colonic stem cells able to mediate cross-tissue plasticity in mature intestines.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colo / Íleo Limite: Animals Idioma: En Revista: Cell Stem Cell Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Colo / Íleo Limite: Animals Idioma: En Revista: Cell Stem Cell Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos