Single cell and genetic analyses reveal conserved populations and signaling mechanisms of gastrointestinal stromal niches

Ji-Eun Kim, Lijiang Fei, Wen-Chi Yin, Sabrina Coquenlorge, Abilasha Rao-Bhatia, Xiaoyun Zhang, Sammy Shun Wai Shi, Ju Hee Lee, Noah A. Hahn, Wasi Rizvi, Kyoung-Han Kim, Hoon-Ki Sung, Chi-chung Hui, Guoji Guo and Tae-Hee Kim ()
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Ji-Eun Kim: The Hospital for Sick Children, Toronto
Lijiang Fei: Zhejiang University of School of Medicine
Wen-Chi Yin: The Hospital for Sick Children, Toronto
Sabrina Coquenlorge: The Hospital for Sick Children, Toronto
Abilasha Rao-Bhatia: The Hospital for Sick Children, Toronto
Xiaoyun Zhang: The Hospital for Sick Children, Toronto
Sammy Shun Wai Shi: The Hospital for Sick Children, Toronto
Ju Hee Lee: The Hospital for Sick Children, Toronto
Noah A. Hahn: The Hospital for Sick Children, Toronto
Wasi Rizvi: The Hospital for Sick Children, Toronto
Kyoung-Han Kim: University of Ottawa Heart Institute, Ottawa
Hoon-Ki Sung: The Hospital for Sick Children, Toronto
Chi-chung Hui: The Hospital for Sick Children, Toronto
Guoji Guo: Zhejiang University of School of Medicine
Tae-Hee Kim: The Hospital for Sick Children, Toronto

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14058-5

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DOI: 10.1038/s41467-019-14058-5

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