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Spatially restricted stromal Wnt signaling restrains prostate epithelial progenitor growth through direct and indirect mechanisms

Item Type:Article
Title:Spatially restricted stromal Wnt signaling restrains prostate epithelial progenitor growth through direct and indirect mechanisms
Creators Name:Wei, X. and Zhang, L. and Zhou, Z. and Kwon, O.J. and Zhang, Y. and Nguyen, H. and Dumpit, R. and True, L. and Nelson, P. and Dong, B. and Xue, W. and Birchmeier, W. and Taketo, M.M. and Xu, F. and Creighton, C.J. and Ittmann, M.M. and Xin, L.
Abstract:Cell-autonomous Wnt signaling has well-characterized functions in controlling stem cell activity, including in the prostate. While niche cells secrete Wnt ligands, the effects of Wnt signaling in niche cells per se are less understood. Here, we show that stromal cells in the proximal prostatic duct near the urethra, a mouse prostate stem cell niche, not only produce multiple Wnt ligands but also exhibit strong Wnt/β-catenin activity. The non-canonical Wnt ligand Wnt5a, secreted by proximal stromal cells, directly inhibits proliefration of prostate epithelial stem or progenitor cells whereas stromal cell-autonomous canonical Wnt/β-catenin signaling indirectly suppresses prostate stem or progenitor activity via the transforming growth factor β (TGFβ) pathway. Collectively, these pathways restrain the proliferative potential of epithelial cells in the proximal prostatic ducts. Human prostate likewise exhibits spatially restricted distribution of stromal Wnt/β-catenin activity, suggesting a conserved mechanism for tissue patterning. Thus, this study shows how distinct stromal signaling mechanisms within the prostate cooperate to regulate tissue homeostasis.
Keywords:Wnt, TGFβ, Prostate Stem Cells, Stem Cell Niche, Stromal-Epithelial Interaction, Animals, Mice
Source:Cell Stem Cell
ISSN:1934-5909
Publisher:Cell Press (U.S.A.)
Volume:24
Number:5
Page Range:753-768
Date:2 May 2019
Official Publication:https://doi.org/10.1016/j.stem.2019.03.010
PubMed:View item in PubMed

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