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Abstract：
YAP plays a vital role in controlling growth and differentiation in various cell lineages. Although the expression of YAP in mice testicular and spermatogenic cells suggests its role in mammalian spermatogenesis, the role of YAP in the development of human male germ cells has not yet been determined. Using an in vitro model and a gene editing approach, we generated human spermatogonia stem cell-like cells (hSSLCs) from human embryonic stem cells (hESCs) and investigated the role of YAP in human spermatogenesis. The results showed that reducing YAP expression during the early stage of spermatogenic differentiation increased the number of PLZF+ hSSLCs and haploid spermatid-like cells. We also demonstrated that the up-regulation of YAP is essential for maintaining spermatogenic cell survival during the later stages of spermatogenic differentiation. The expression of YAP that deviates from this pattern results in a lower number of hSSLCs and an increased level of spermatogenic cell death. Taken together, our result demonstrates that the dynamic expression pattern of YAP is essential for human spermatogenesis. Modulating the level of YAP during human spermatogenesis could improve the production yield of male germ cells derived from hESCs, which could provide the optimization method for in vitro gametogenesis and gain insight into the application in the treatment of male infertility.
摘要：
YAP在控制各种细胞系的生长和分化中起着至关重要的作用。尽管YAP在小鼠睾丸和生精细胞中的表达表明其在哺乳动物精子发生中的作用，YAP在人类男性生殖细胞发育中的作用尚未确定。使用体外模型和基因编辑方法，我们从人胚胎干细胞(hESCs)产生了人精原细胞干细胞样细胞(hSSLCs),并研究了YAP在人精子发生中的作用.结果表明，在生精分化早期降低YAP表达会增加PLZFhSSLCs和单倍体精子细胞的数量。我们还证明，在生精分化的后期，YAP的上调对于维持生精细胞的存活至关重要。偏离该模式的YAP的表达导致较低数量的hSSLCs和较高水平的生精细胞死亡。一起来看,我们的结果表明，YAP的动态表达模式对人类精子发生至关重要。在人类精子发生过程中调节YAP的水平可以提高源自hESCs的雄性生殖细胞的产量，为体外配子的发生提供了优化方法,深入了解其在男性不育治疗中的应用。
