Laboratory of Pathology and Development, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan.
Molecular and Behavioral Neurobiology, Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany.
Sci Rep. 2019 Apr 15;9(1):6063. doi: 10.1038/s41598-019-42578-z.
Gonocyte-to-spermatogonia transition is a critical fate determination process to initiate sperm production throughout the lifecycle. However, the molecular dynamics of this process has not been fully elucidated mainly due to the asynchronized differentiation stages of neonatal germ cells. In this study, we employed single cell RNA sequencing analyses of P1.5-5.5 germ cells to clarify the temporal dynamics of gene expression during gonocyte-to-spermatogonia transition. The analyses identified transcriptional modules, one of which regulates spermatogonial gene network in neonatal germ cells. Among them, we identified Dec2, a bHLH-type transcription factor, as a transcriptional repressor for a spermatogonial differentiation factor Sohlh1. Deficiency of Dec2 in mice induces significant reduction of undifferentiated spermatogonia, and transplantation assay using Dec2-depleted cells also demonstrated the impaired efficiency of engraftment, suggesting its role in maintaining spermatogonial stem cells (SSCs). Collectively, this study revealed the intrinsic role of a new SSC factor Dec2, which protects germ cells from inadequate differentiation during neonatal testis development.
精原细胞向精原细胞的转变是启动整个生命周期精子发生的关键命运决定过程。然而，由于新生生殖细胞的分化阶段不同步，这个过程的分子动力学尚未完全阐明。在这项研究中，我们对 P1.5-5.5 天的生殖细胞进行了单细胞 RNA 测序分析，以阐明精原细胞向精原细胞转变过程中基因表达的时间动态。分析确定了转录模块，其中一个模块调节新生生殖细胞中的精原细胞基因网络。其中，我们鉴定出 Dec2 是一种 bHLH 型转录因子，作为精原细胞分化因子 Sohlh1 的转录抑制剂。Dec2 缺失的小鼠会导致未分化的精原细胞显著减少，使用 Dec2 耗尽的细胞进行移植实验也表明植入效率受损，提示其在维持精原干细胞 (SSC) 中的作用。总之，这项研究揭示了新的 SSC 因子 Dec2 的内在作用，它可以保护生殖细胞在新生睾丸发育过程中免受不适当的分化。
