生物
RNA剪接
祖细胞
细胞生物学
转录组
选择性拼接
生殖细胞
细胞周期
精子发生
有丝分裂
祖细胞
拼接因子
干细胞
遗传学
细胞
核糖核酸
基因
基因表达
信使核糖核酸
内分泌学
作者
Wenbo Liu,Xukun Lu,Ziran Zhao,Qiannan Li,Yue Xue,Zheng Gao,Simin Sun,Wen‐Long Lei,Lei Li,Geng An,Hanyan Liu,Zhiming Han,Ying‐Chun Ouyang,Yi Hou,Zhenbo Wang,Qingyuan Sun,Jianqiao Liu
标识
DOI:10.1101/2022.03.06.483179
摘要
Abstract Alternative splicing expands the transcriptome and proteome complexity and plays essential roles in tissue development and human diseases. However, how alternative splicing regulates spermatogenesis remains largely unknown. Here, using germ cell-specific knockout mouse model, we demonstrated that the splicing factor Srsf10 is essential for spermatogenesis and male fertility. Depletion of Srsf10 in germ cells had little effect on the formation of SSCs but impeded the expansion of progenitor spermatogonia, leading to the failure of spermatogonia differentiation and meiosis initiation. This was further evidenced by the decreased expression of progenitor cell markers in bulk RNA-seq, and much less progenitor and differentiating spermatogonia in single-cell RNA-seq data. Furthermore, the expression of genes involved in cell cycle was abnormal in all subtypes of spermatogonia identified in single-cell RNA-seq data. Notably, using isolated spermatogonia, we found that Srsf10 depletion disturbed the alternative splicing of hundreds of genes, which were preferentially associated with cell cycle, mitotic cell cycle checkpoint and germ cell development, including Dazl , Kit , Ret , Sycp1 , Nasp and Bor a. These data suggest that SRSF10 is critical for the expansion of progenitor spermatogonia by regulating alternative splicing, expanding our understanding of the mechanism underlying spermatogenesis.
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