Cell stem cell · 2021
SATB2 preserves colon stem cell identity and mediates ileum-colon conversion via enhancer remodeling.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
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
Аннотация
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.