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USP11 regulates proliferation and apoptosis of human spermatogonial stem cells via HOXC5-mediated canonical WNT/ß-catenin signaling pathway.
Gao, Jun; Xu, Zhipeng; Song, Weijie; Huang, Jiwei; Liu, Wei; He, Zuping; He, Leye.
Afiliação
  • Gao J; Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, China.
  • Xu Z; Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, China.
  • Song W; Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, China.
  • Huang J; Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, China.
  • Liu W; Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, School of Medicine, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University, Changsha, Hunan, 410013, China.
  • He Z; Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410011, China.
  • He L; Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, School of Medicine, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University, Changsha, Hunan, 410013, China. zupinghe@hunnu.edu.cn.
Cell Mol Life Sci ; 81(1): 211, 2024 May 09.
Article em En | MEDLINE | ID: mdl-38722330
ABSTRACT
Spermatogonial stem cells (SSCs) are capable of transmitting genetic information to the next generations and they are the initial cells for spermatogenesis. Nevertheless, it remains largely unknown about key genes and signaling pathways that regulate fate determinations of human SSCs and male infertility. In this study, we explored the expression, function, and mechanism of USP11 in controlling the proliferation and apoptosis of human SSCs as well as the association between its abnormality and azoospermia. We found that USP11 was predominantly expressed in human SSCs as shown by database analysis and immunohistochemistry. USP11 silencing led to decreases in proliferation and DNA synthesis and an enhancement in apoptosis of human SSCs. RNA-sequencing identified HOXC5 as a target of USP11 in human SSCs. Double immunofluorescence, Co-immunoprecipitation (Co-IP), and molecular docking demonstrated an interaction between USP11 and HOXC5 in human SSCs. HOXC5 knockdown suppressed the growth of human SSCs and increased apoptosis via the classical WNT/ß-catenin pathway. In contrast, HOXC5 overexpression reversed the effect of proliferation and apoptosis induced by USP11 silencing. Significantly, lower levels of USP11 expression were observed in the testicular tissues of patients with spermatogenic disorders. Collectively, these results implicate that USP11 regulates the fate decisions of human SSCs through the HOXC5/WNT/ß-catenin pathway. This study thus provides novel insights into understanding molecular mechanisms underlying human spermatogenesis and the etiology of azoospermia and it offers new targets for gene therapy of male infertility.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Espermatogênese / Tioléster Hidrolases / Apoptose / Proliferação de Células / Via de Sinalização Wnt Limite: Humans / Male Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Espermatogênese / Tioléster Hidrolases / Apoptose / Proliferação de Células / Via de Sinalização Wnt Limite: Humans / Male Idioma: En Ano de publicação: 2024 Tipo de documento: Article