Sertoli cell-derived exosomal MicroRNA-486-5p regulates differentiation of spermatogonial stem cell through PTEN in mice.
Sertoli cell-derived exosomal MicroRNA-486-5p regulates differentiation of spermatogonial stem cell through PTEN in mice.
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支持细胞衍生的外泌体 MicroRNA-486-5p 通过 PTEN 调节小鼠精原干细胞的分化
DOI：
10.1111/jcmm.16347
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发表时间：
2021-04
影响因子：
5.3
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Li Q;Li H;Liang J;Mei J;Cao Z;Zhang L;Luo J;Tang Y;Huang R;Xia H;Zhang Q;Xiang Q;Yang Y;Huang Y
精原干细胞（spermatogonial stem cell，SSC）的自我更新和分化对男性生育和生殖至关重要，而这两者都受到睾丸微环境的高度调节。外泌体miRNA已成为细胞间通讯的新成分。然而，它们在区分南南合作方面的作用仍不清楚。在这里，我们观察到miR-486 - 5 p在支持细胞和支持细胞来源的外泌体中富集。外泌体介导miR-486 - 5 p从Sertoli细胞转移到SSC。外泌体释放miR-486 - 5 p，从而上调Stra 8的表达（由视黄酸8刺激）并促进SSC的分化。PTEN被鉴定为miR-486 - 5 p的靶点。miR-486 - 5 p在SSCs中的过表达下调了PTEN的表达，其上调了STRA 8和SYCP 3的表达，促进了SSCs的分化。此外，阻断外泌体介导的miR-486 - 5 p转移可抑制SSC的分化。我们的研究结果表明，miR-486 - 5 p作为支持细胞和精原干细胞之间的通讯分子，调节精原干细胞的分化。这为阐明调控SSC分化的分子机制提供了新的见解，并为男性不育的诊断、治疗和预防提供了依据。
Self‐renewal and differentiation of spermatogonial stem cell (SSC) are critical for male fertility and reproduction, both of which are highly regulated by testicular microenvironment. Exosomal miRNAs have emerged as new components in intercellular communication. However, their roles in the differentiation of SSC remain unclear. Here, we observed miR‐486‐5p enriched in Sertoli cell and Sertoli cell‐derived exosomes. The exosomes mediate the transfer of miR‐486‐5p from Sertoli cells to SSCs. Exosomes release miR‐486‐5p, thus up‐regulate expression of Stra8 (stimulated by retinoic acid 8) and promote differentiation of SSC. And PTEN was identified as a target of miR‐486‐5p. Overexpression of miR‐486‐5p in SSCs down‐regulates PTEN expression, which up‐regulates the expression of STRA8 and SYCP3, promotes SSCs differentiation. In addition, blocking the exosome‐mediated transfer of miR‐486‐5p inhibits differentiation of SSC. Our findings demonstrate that miR‐486‐5p acts as a communication molecule between Sertoli cells and SSCs in modulating differentiation of SSCs. This provides a new insight on molecular mechanisms that regulates SSC differentiation and a basis for the diagnosis, treatment, and prevention of male infertility.
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支持细胞衍生的外泌体 MicroRNA-486-5p 通过 PTEN 调节小鼠精原干细胞的分化
影响因子：
5.3
作者：
Li Q;Li H;Liang J;Mei J;Cao Z;Zhang L;Luo J;Tang Y;Huang R;Xia H;Zhang Q;Xiang Q;Yang Y;Huang Y
通讯作者：
Huang Y
影响因子：
4.1
作者：
Hofmann, Marie-Claude
通讯作者：
Hofmann, Marie-Claude
影响因子：
4
作者：
Planchon, Sarah M.;Waite, Kristin A.;Eng, Charis
通讯作者：
Eng, Charis
影响因子：
2.5
作者：
De Rooij, Dirk G.
通讯作者：
De Rooij, Dirk G.
影响因子：
4
作者：
He, Yanfa;Liu, Jianzhen;Liu, Ying
通讯作者：
Liu, Ying