Dataset Information

Spatially Restricted Stromal Wnt Signaling Restrains Prostate Epithelial Progenitor Growth through Direct and Indirect Mechanisms.

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/?-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/?-catenin signaling indirectly suppresses prostate stem or progenitor activity via the transforming growth factor ? (TGF?) 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/?-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.

SUBMITTER: Wei X

PROVIDER: S-EPMC6548441 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Spatially Restricted Stromal Wnt Signaling Restrains Prostate Epithelial Progenitor Growth through Direct and Indirect Mechanisms.

Wei Xing X Zhang Li L Zhou Zhicheng Z Kwon Oh-Joon OJ Zhang Yiqun Y Nguyen Hoang H Dumpit Ruth R True Lawrence L Nelson Peter P Dong Baijun B Xue Wei W Birchmeier Walter W Taketo Makoto M MM Xu Feng F Creighton Chad J CJ Ittmann Michael M MM Xin Li L

Cell stem cell 20190411 5

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 strom ...[more]

PMID: 30982770

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Project description:Quantifying spatiotemporally explicit interactions within animal populations facilitates the understanding of social structure and its relationship with ecological processes. Data from animal tracking technologies (Global Positioning Systems ["GPS"]) can circumvent longstanding challenges in the estimation of spatiotemporally explicit interactions, but the discrete nature and coarse temporal resolution of data mean that ephemeral interactions that occur between consecutive GPS locations go undetected. Here, we developed a method to quantify individual and spatial patterns of interaction using continuous-time movement models (CTMMs) fit to GPS tracking data. We first applied CTMMs to infer the full movement trajectories at an arbitrarily fine temporal scale before estimating interactions, thus allowing inference of interactions occurring between observed GPS locations. Our framework then infers indirect interactions-individuals occurring at the same location, but at different times-while allowing the identification of indirect interactions to vary with ecological context based on CTMM outputs. We assessed the performance of our new method using simulations and illustrated its implementation by deriving disease-relevant interaction networks for two behaviorally differentiated species, wild pigs (Sus scrofa) that can host African Swine Fever and mule deer (Odocoileus hemionus) that can host chronic wasting disease. Simulations showed that interactions derived from observed GPS data can be substantially underestimated when temporal resolution of movement data exceeds 30-min intervals. Empirical application suggested that underestimation occurred in both interaction rates and their spatial distributions. CTMM-Interaction method, which can introduce uncertainties, recovered majority of true interactions. Our method leverages advances in movement ecology to quantify fine-scale spatiotemporal interactions between individuals from lower temporal resolution GPS data. It can be leveraged to infer dynamic social networks, transmission potential in disease systems, consumer-resource interactions, information sharing, and beyond. The method also sets the stage for future predictive models linking observed spatiotemporal interaction patterns to environmental drivers.

Dataset Information

Spatially Restricted Stromal Wnt Signaling Restrains Prostate Epithelial Progenitor Growth through Direct and Indirect Mechanisms.

Publications

Spatially Restricted Stromal Wnt Signaling Restrains Prostate Epithelial Progenitor Growth through Direct and Indirect Mechanisms.

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