Citation

Gu 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. 2021. SATB2 preserves colon stem cell identity and mediates ileum-colon conversion via enhancer remodeling. Cell stem cell. Pubmed: 34582804 DOI:10.1016/j.stem.2021.09.004

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.
Copyright © 2021 Elsevier Inc. All rights reserved.

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Rich Lee seeks to understand heart failure and metabolic diseases that accompany human aging, and translate that understanding into therapies. Lee is an active clinician, regularly treating patients at Brigham and Women’s Hospital.

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