4.7 Article

SATB2 preserves colon stem cell identity and mediates ileum-colon conversion via enhancer remodeling

期刊

CELL STEM CELL
卷 29, 期 1, 页码 101-+

出版社

CELL PRESS
DOI: 10.1016/j.stem.2021.09.004

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资金

  1. Weill Cornell Medicine funds
  2. Tri-Institutional Stem Cell grant
  3. NIH/NIDDK [1R01DK125817, 1R01DK082889, 1R01DK107396, R01DK121915]
  4. NNF Center grant for stem cell biology [NNF17CC0027852]
  5. MSKCC support grant [NIH P30 CA008748]
  6. Deutsche Forschungsgemeinschaft (DFG) [KR 5451/1-1]

向作者/读者索取更多资源

SATB2 plays a crucial role in maintaining the identity of adult colonic stem cells and epithelial cells in mice and humans.
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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