2. Academic Validation
  3. YAP is required for prostate development, regeneration, and prostate stem cell function

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

  • Cell Death Discov. 2023 Sep 9;9(1):339. doi: 10.1038/s41420-023-01637-1.
Hui Xie # 1,  Linpei Guo # 2,  Qianwang Ma # 1,  Wenyi Zhang 3,  Zhao Yang 1,  Zhun Wang 1,  Shuanghe Peng 4,  Keruo Wang 1,  Simeng Wen 1,  Zhiqun Shang 5,  Yuanjie Niu 6
Affiliations

Affiliations

  • 1 Department of Urology, Tianjin Institute of Urology, The second hospital of Tianjin Medical University, 300211, Tianjin, China.
  • 2 Gene and Immunotherapy Center, The Second Hospital of Shandong University, 250033, Jinan, Shandong, China.
  • 3 Department of Radiology, The second hospital of Tianjin Medical University, 300211, Tianjin, China.
  • 4 Department of Pathology, Tianjin Institute of Urology, The second hospital of Tianjin Medical University, 300211, Tianjin, China.
  • 5 Department of Urology, Tianjin Institute of Urology, The second hospital of Tianjin Medical University, 300211, Tianjin, China. zhiqun_shang@tmu.edu.cn.
  • 6 Department of Urology, Tianjin Institute of Urology, The second hospital of Tianjin Medical University, 300211, Tianjin, China. niuyuanjie68@163.com.
  • # Contributed equally.
PMID: 37689711 DOI: 10.1038/s41420-023-01637-1
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.

Figures
Products
Inhibitors & Agonists
Other Products