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

한빛사논문

조회1,837

The Hospital for Sick Children, University of Toronto

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Nat. Commun., Published17 January 2020, 11, Article number: 334 | DOI https://doi.org/10.1038/s41467-019-14058-5 Single cell and genetic analyses reveal conserved populations and signaling mechanisms of gastrointestinal stromal niches

Ji-Eun Kim^1,2, Lijiang Fei³, Wen-Chi Yin^1,2, Sabrina Coquenlorge^1,2, Abilasha Rao-Bhatia^1,2, Xiaoyun Zhang^1,2, Sammy Shun Wai Shi^4,5, Ju Hee Lee^4,5, Noah A. Hahn^1,2, Wasi Rizvi^1,2, Kyoung-Han Kim^6,7, Hoon-Ki Sung^4,5, Chi-chung Hui^1,2, Guoji Guo³& Tae-Hee Kim^1,2,*

¹ Program 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.
³Center for Stem Cell and Regenerative Medicine, Zhejiang University of School of Medicine, Hangzhou 310058, China. 4 Translation Medicine Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
⁵Department of Laboratory Medicine and Pathobiology, University of Toronto, ON M5S 1A8, Canada.
⁶University of Ottawa Heart Institute, Ottawa, ON K1Y 4W7, Canada.
⁷ Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada

^*Correspondence to Tae-Hee Kim.

Abstract

Stomach and intestinal stem cells are located in discrete niches called the isthmus and crypt, respectively. Recent studies have demonstrated a surprisingly conserved role for Wnt signaling in gastrointestinal development. Although intestinal stromal cells secrete Wnt ligands to promote stem cell renewal, the source of stomach Wnt ligands is still unclear. Here, by performing single cell analysis, we identify gastrointestinal stromal cell populations with transcriptome signatures that are conserved between the stomach and intestine. In close proximity to epithelial cells, these perictye-like cells highly express telocyte and pericyte markers as well as Wnt ligands, and they are enriched for Hh signaling. By analyzing mice activated for Hh signaling, we show a conserved mechanism of GLI2 activation of Wnt ligands. Moreover, genetic inhibition of Wnt secretion in perictye-like stromal cells or stromal cells more broadly demonstrates their essential roles in gastrointestinal regeneration and development, respectively, highlighting a redundancy in gastrointestinal stem cell niches.

논문정보

형식Research article
게재일2020년 01월 (BRIC 등록일 2020-01-22)
연구진국외 연구진
분야 생명과학 > 분자생물학

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