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SATB2 维持结肠干细胞特性，并通过增强子重塑介导回肠-结肠转化。

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

机构信息

Division of Regenerative Medicine & Ansary Stem Cell Institute, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.

Cell Biology Program and Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, 430 E 67th Street, New York, NY 10065, USA.

出版信息

Cell Stem Cell. 2022 Jan 6;29(1):101-115.e10. doi: 10.1016/j.stem.2021.09.004. Epub 2021 Sep 27.

DOI:10.1016/j.stem.2021.09.004
PMID:34582804
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8741647/
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.

摘要

成体干细胞通过产生组织特异性祖细胞来维持组织的结构和功能，但维持其组织特性的因素尚不清楚。小肠和大肠在细胞组成和功能上有明显的差异，这反映了它们不同的干细胞群体。在这里，我们发现 SATB2，一种结肠特异性染色质因子，能够在小鼠和人类中特异性地维持 LGR5 成体结肠干细胞和上皮细胞的特性。成年小鼠中 Satb2 的缺失会导致结肠干细胞稳定地转化为小肠回肠样干细胞，并将结肠黏膜替换为类似于回肠的组织。相反，SATB2 赋予了小鼠回肠的结肠特性。人类结肠类器官在 SATB2 缺失后也会呈现出回肠特征。SATB2 通过调节肠转录因子 CDX2 和 HNF4A 的增强子结合来调节结肠的特性。我们的研究揭示了一种保守的结肠干细胞核心调控因子，它能够介导成熟肠道中的跨组织可塑性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5613/8741647/64cff98b8437/nihms-1739927-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5613/8741647/b15754842c7d/nihms-1739927-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5613/8741647/a797b28855c7/nihms-1739927-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5613/8741647/00865fec074c/nihms-1739927-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5613/8741647/4f924b7a542b/nihms-1739927-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5613/8741647/e860a081818c/nihms-1739927-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5613/8741647/967a3171af88/nihms-1739927-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5613/8741647/64cff98b8437/nihms-1739927-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5613/8741647/b15754842c7d/nihms-1739927-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5613/8741647/a797b28855c7/nihms-1739927-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5613/8741647/00865fec074c/nihms-1739927-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5613/8741647/4f924b7a542b/nihms-1739927-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5613/8741647/e860a081818c/nihms-1739927-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5613/8741647/967a3171af88/nihms-1739927-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5613/8741647/64cff98b8437/nihms-1739927-f0008.jpg

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