Stromal Hippo-YAP signaling in stem cell niche controls intestinal homeostasis [preprint]
Authors
Dang, KyvanSingh, Alka
Cotton, Jennifer L.
Tao, Zhipeng
Liu, Haibo
Zhu, Lihua J.
Wu, Xu
Mao, Junhao
UMass Chan Affiliations
Molecular, Cell and Cancer BiologyDocument Type
PreprintPublication Date
2022-05-12
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Intestinal homeostasis is tightly regulated by the reciprocal interaction between gut epithelium and adjacent mesenchyme. The mammalian Hippo-YAP pathway is intimately associated with intestinal epithelial homeostasis and re-generation; however, its role in postnatal gut mesenchyme remains poorly defined. We find that, although removal of the core Hippo kinases Lats1/2 or activation of YAP in adult intestinal smooth muscle has largely no effect; Hippo-YAP signaling in Gli1/PDGFR-expressing intestinal stromal cells is critical to maintain the stem cell niche. We show that YAP/TAZ activation drives over-proliferation and suppresses smooth muscle actin expression in the niche-forming Gli1+ mesenchymal progenitors. In addition, mesenchymal YAP/TAZ activation disrupts the epithelial-mesenchymal crosstalk by promoting Wnt ligand production, leading to epithelial Wnt pathway activation. Our data also reveal that YAP/TAZ are upregulated in the stroma during DSS-induced injury and stromal YAP activation promotes intestinal epithelial regeneration. Altogether, our data identify an essential requirement for stromal Hippo-YAP signaling in the stem cell niche during intestinal homeostasis.Source
Stromal Hippo-YAP signaling in stem cell niche controls intestinal homeostasis Kyvan Dang, Alka Singh, Jennifer L. Cotton, Zhipeng Tao, Haibo Liu, Lihua J. Zhu, Xu Wu, Junhao Mao bioRxiv 2022.05.12.491640; doi: https://doi.org/10.1101/2022.05.12.491640DOI
10.1101/2022.05.12.491640Permanent Link to this Item
http://hdl.handle.net/20.500.14038/51457Notes
This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.Rights
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.; Attribution 4.0 InternationalDistribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1101/2022.05.12.491640
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Except where otherwise noted, this item's license is described as The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.