The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Hunan Normal University School of Medicine, 371 Tongzipo Road, Changsha, Hunan 410013, China.
The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Hunan Normal University School of Medicine, 371 Tongzipo Road, Changsha, Hunan 410013, China.
Semin Cell Dev Biol. 2022 Jan;121:32-39. doi: 10.1016/j.semcdb.2021.05.003. Epub 2021 May 24.
Human spermatogonial stem cells (SSCs) and Sertoli cells might have the applications in reproduction and regenerative medicine. Abnormal spermatogenesis results in male infertility, which seriously affects human reproduction and health. Spermatogenesis depends on the epigenetic and genetic regulation of male germ cells and somatic cells. A number of microRNAs (miRNAs) have been identified in human testicular tissues, and they are closely related to male fertility. Significantly, we and peers have recently demonstrated that numerous miRNAs are essential for regulating the self-renewal and apoptosis of human SSCs and Sertoli cells through controlling their mRNA and lncRNA targets. In this review, we critically discuss these findings regarding the important functions and mechanisms of miRNAs in mediating the fate determinations of human SSCs and Sertoli cells. Meanwhile, we illustrate the regulatory networks for miRNAs by forming the upstream and downstream regulators of mRNAs and lncRNAs in human SSCs, and we address that miRNAs regulate the decisions of Sertoli cells by targeting genes and via N6-methyladenosine (m6A). We also point out the future directions for further studies on this field. This review could offer an update on novel molecular targets for treating male infertility and new insights into epigenetic regulation of human spermatogenesis.
人类精原干细胞 (SSCs) 和支持细胞在生殖和再生医学中可能具有应用价值。异常的精子发生会导致男性不育，严重影响人类的生殖和健康。精子发生依赖于雄性生殖细胞和体细胞的表观遗传和遗传调控。在人类睾丸组织中已经鉴定出许多 microRNAs（miRNAs），它们与男性生育能力密切相关。值得注意的是，我们和同行最近证明，许多 miRNAs 通过控制其 mRNA 和 lncRNA 靶标，对于调节人类 SSCs 和支持细胞的自我更新和凋亡至关重要。在这篇综述中，我们批判性地讨论了这些发现，这些发现涉及 miRNA 在介导人类 SSCs 和支持细胞命运决定中的重要功能和机制。同时，我们通过形成人类 SSCs 中 mRNA 和 lncRNA 的上游和下游调节剂来阐明 miRNA 的调控网络，并指出 miRNA 通过靶向基因和通过 N6-甲基腺苷 (m6A) 来调节支持细胞的决策。我们还指出了该领域进一步研究的未来方向。这篇综述可以为治疗男性不育症提供新的分子靶标，并深入了解人类精子发生的表观遗传调控。
