YAP is required for prostate development, regeneration, and prostate stem cell function

Abstract

Prostate development and regeneration depend on prostate stem cell function, the delicate balance of stem cell self-renewal and differentiation. However, mechanisms modulating prostate stem cell function remain poorly identified. Here, we explored the roles of Yes-associated protein 1 (YAP) in prostate stem cells, prostate development and regeneration. Using YAPfl/fl, CD133-CreER mice, we found that stem cell-specific YAP-deficient mice had compromised branching morphogenesis and epithelial differentiation, resulting in damaged prostate development. YAP inhibition also significantly affected the regeneration process of mice prostate, leading to impaired regenerated prostate. Furthermore, YAP ablation in prostate stem cells significantly reduced its self-renewal activity in vitro, and attenuated prostate regeneration of prostate grafts in vivo. Further analysis revealed a decrease in Notch and Hedgehog pathways expression in YAP inhibition cells, and treatment with exogenous Shh partially restored the self-renewal ability of prostate sphere cells. Taken together, our results revealed the roles of YAP in prostate stem cell function and prostate development and regeneration through regulation of the Notch and Hedgehog signaling pathways.

Conserved signals orchestrate self-organization and symmetry breaking of bi-layered epithelia during development and regeneration

“…While YAP was shown to be functionally dispensable for the homeostasis of the virgin MG (Q. , transient activation of YAP or inactivation of Lats1/2 in adult MG LCs led to reactivation of the expression of some basal markers, notably K14 (Kern et al, 2022;Panciera et al, 2016). In the adult prostate, YAP knock-out displayed a weak phenotype, but genetic deletion during embryonic branching morphogenesis or prostate regeneration upon castration drastically affected both processes (Xie et al, 2023). Similarly, in the developing SG, YAP deletion resulted in defects in branching morphogenesis, while its forced activation promoted the expansion of cells in the salivary ductal compartment (Szymaniak et al, 2017).…”