关键词: Sertoli cell maturation retinoic acid signaling single cell RNA-sequencing spermatogenesis

来  源:   DOI:10.1093/biolre/ioae115

Abstract:
Sertoli cells, omnipresent, somatic cells within the seminiferous tubules of the mammalian testis are essential to male fertility. Sertoli cells maintain the integrity of the testicular microenvironment, regulate hormone synthesis, and of particular importance, synthesize the active derivative of vitamin A, all trans retinoic acid (atRA), which is required for germ cell differentiation and the commitment of male germ cells to meiosis. Stages VIII-IX, when atRA synthesis occurs in the testis, coincides with multiple germ cell development and testicular restructuring events that rely on Sertoli cell gene products to proceed normally. In this study, we have synchronized and captured the mouse testis at four recurrent points of atRA synthesis to observe transcriptomic changes within Sertoli cells as mice age and the Sertoli cells are exposed to increasingly developed germ cell subtypes. This work provides comprehensive, high-resolution characterization of the timing of induction of functional Sertoli cell genes across the first wave of spermatogenesis, and outlines in silico predictions of germ cell derived signaling mechanisms targeting Sertoli cells. We have found that Sertoli cells adapt to their environment, especially to the needs of the germ cell populations present and establish germ-Sertoli cell and Sertoli-Sertoli cell junctions early, but gain many of their known immune-regulatory and protein secretory functions in preparation for spermiogenesis and spermiation. Additionally, we have found unique patterns of germ-Sertoli signaling present at each endogenous pulse of atRA, suggesting individual functions of the various germ cells in germ-Sertoli communication.
摘要:
支持细胞,无所不在,哺乳动物睾丸生精管内的体细胞对男性生育力至关重要。支持细胞维持睾丸微环境的完整性,调节激素合成,特别重要的是,合成维生素A的活性衍生物,全反式维甲酸(atRA),这是生殖细胞分化和雄性生殖细胞减数分裂的承诺所必需的。第八至九阶段,当ATRA合成发生在睾丸中时,与依赖支持细胞基因产物正常进行的多个生殖细胞发育和睾丸重组事件相吻合。在这项研究中,我们在atRA合成的四个复发点同步并捕获了小鼠睾丸,以观察随着小鼠年龄增长和Sertoli细胞暴露于越来越发达的生殖细胞亚型时Sertoli细胞内的转录组变化.这项工作提供了全面,在精子发生的第一波中,功能性支持细胞基因的诱导时间的高分辨率表征,并概述了针对支持细胞的生殖细胞衍生信号机制的计算机预测。我们发现支持细胞能够适应环境,特别是对生殖细胞群的存在和早期建立的生殖细胞和Sertoli-Sertoli细胞连接的需求,但获得了许多已知的免疫调节和蛋白质分泌功能,为精子形成和精子形成做准备。此外,我们已经发现了独特的细菌-Sertoli信号模式存在于每个内源性脉冲的atRA,表明各种生殖细胞在胚芽-Sertoli通讯中的个体功能。
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