Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-14058-5
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Funding
- SickKids Foundation
- University of Toronto's Medicine by Design Initiative/the Canada First Research Excellence Fund
- Canadian Institutes of Health Research (CIHR) [PJT 155923]
- Natural Science Research Council of Canada (NSERC) [RGPIN-2016-06093]
- CIHR [PJT 162083]
- University of Toronto
- SickKids Restracomp graduate student fellowships
- NSERC
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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. Wnt signals for intestinal stem cell self-renewal originate from the stroma and Paneth cells, but the source in stomach is unclear. Here the authors identify a conserved population of stromal cells adjacent to stomach epithelia where Gli2 activates Wnt ligands to promote gastrointestinal regeneration and development.
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