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

TitleSATB2 preserves colon stem cell identity and mediates ileum-colon conversion via enhancer remodeling.
Publication TypeJournal Article
Year of Publication2021
AuthorsGu W, Wang H, Huang X, Kraiczy J, Singh PNP, Ng C, Dagdeviren S, Houghton S, Pellon-Cardenas O, Lan Y, Nie Y, Zhang J, Banerjee KK, Onufer EJ, Warner BW, Spence J, Scherl E, Rafii S, Lee RT, Verzi MP, Redmond D, Longman R, Helin K, Shivdasani RA, Zhou Q
JournalCell Stem Cell
Date Published2021 Sep 22
ISSN1875-9777
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.

DOI10.1016/j.stem.2021.09.004
Alternate JournalCell Stem Cell
PubMed ID34582804
Grant ListR01 DK121915 / DK / NIDDK NIH HHS / United States