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

Wei Gu, Hua Wang, Xiaofeng Huang, Judith Kraiczy, Pratik N.P. Singh, Charles Ng, Sezin Dagdeviren, Sean Houghton, Oscar Pellon-Cardenas, Ying Lan, Yaohui Nie, Jiaoyue Zhang, Kushal K. Banerjee, Emily J. Onufer, Brad W. Warner, Jason Spence, Ellen Scherl, Shahin Rafii, Richard T. Lee, Michael P. VerziDavid Redmond, Randy Longman, Kristian Helin, Ramesh A. Shivdasani, Qiao Zhou

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish
Pages (from-to)101-115.e10
JournalCell Stem Cell
Volume29
Issue number1
DOIs
StatePublished - Jan 6 2022

Keywords

  • SATB2, intestine regeneration, colonic mucosa, stem cell conversion, enhancer remodelingintestine

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