김태희 (The Hospital for Sick Children, University of Toronto)

한빛사논문

조회473

The Hospital for Sick Children, University of Toronto

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Nat. Commun., 2023 Jan 30;14(1):497 | doi: 10.1038/s41467-023-36228-2 Epigenetic control of cellular crosstalk defines gastrointestinal organ fate and function

Ryan J Smith ^{# 1,2}, Minggao Liang ^{# 2,3}, Adrian Kwan Ho Loe ^1,2, Theodora Yung ^1,2, Ji-Eun Kim ^1,2, Matthew Hudson ^2,3, Michael D Wilson ^2,3, Tae-Hee Kim ^4,5

¹Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada.
²Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.
³Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada.
⁴Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada.
⁵Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.
^#Contributed equally.

Corresponding author: Correspondence to Tae-Hee Kim.

Abstract

Epithelial-mesenchymal signaling in the gastrointestinal system is vital in establishing regional identity during organogenesis and maintaining adult stem cell homeostasis. Although recent work has demonstrated that Wnt ligands expressed by mesenchymal cells are required during gastrointestinal development and stem cell homeostasis, epigenetic mechanisms driving spatiotemporal control of crosstalk remain unknown. Here, we demonstrate that gastrointestinal mesenchymal cells control epithelial fate and function through Polycomb Repressive Complex 2-mediated chromatin bivalency. We find that while key lineage-determining genes possess tissue-specific chromatin accessibility, Polycomb Repressive Complex 2 controls Wnt expression in mesenchymal cells without altering accessibility. We show that reduction of mesenchymal Wnt secretion rescues gastrointestinal fate and proliferation defects caused by Polycomb Repressive Complex 2 loss. We demonstrate that mesenchymal Polycomb Repressive Complex 2 also regulates niche signals to maintain stem cell function in the adult intestine. Our results highlight a broadly permissive chromatin architecture underlying regionalization in mesenchymal cells, then demonstrate further how chromatin architecture in niches can influence the fate and function of neighboring cells.

논문정보

형식Research article
게재일2023년 01월 (BRIC 등록일 2023-02-01)
연구진국외 연구진
분야 생명과학 > 분자생물학

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