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

Hui Xie1, Linpei Guo2, Qianwang Ma1

  • 1Department of Urology, Tianjin Institute of Urology, The second hospital of Tianjin Medical University, 300211, Tianjin, China.

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Yes-associated protein 1 (YAP) is crucial for prostate stem cell function, impacting prostate development and regeneration. YAP deficiency impairs stem cell self-renewal and regeneration by affecting Notch and Hedgehog pathways.

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Area of Science:

  • Urology
  • Developmental Biology
  • Stem Cell Biology

Background:

  • Prostate development and regeneration rely on prostate stem cell self-renewal and differentiation.
  • Mechanisms controlling prostate stem cell function are not well understood.

Purpose of the Study:

  • To investigate the role of Yes-associated protein 1 (YAP) in prostate stem cells.
  • To elucidate YAP's function in prostate development and regeneration.

Main Methods:

  • Utilized YAP conditional knockout mice (YAPfl/fl, CD133-CreER) for stem cell-specific YAP deficiency.
  • Assessed prostate development, regeneration, and stem cell self-renewal in vitro and in vivo.
  • Analyzed Notch and Hedgehog signaling pathway expression.

Main Results:

  • Stem cell-specific YAP deficiency led to impaired prostate development, including compromised branching morphogenesis and epithelial differentiation.
  • YAP inhibition significantly hindered prostate regeneration and reduced stem cell self-renewal capacity in vitro and in vivo.
  • YAP deficiency decreased Notch and Hedgehog pathway expression; Shh treatment partially restored stem cell self-renewal.

Conclusions:

  • YAP plays a critical role in maintaining prostate stem cell function.
  • YAP regulates prostate development and regeneration by modulating Notch and Hedgehog signaling pathways.