SRSF10 is essential for progenitor spermatogonia expansion by regulating alternative splicing
| Autor: | Ruibao SU, Zheng-Hui Zhao, Xukun Lu, Wenbo Liu, Qian-Nan Li Li, Yue Xue, Zheng Gao, Si-Min Sun Sun, Wen-Long Lei, Lei Li, Geng An, Hanyan Liu, Zhiming Han, Ying-Chun Ouyang, Yi Hou, Zhen-Bo Wang, Qing-Yuan Sun, Jianqiao Liu |
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| Rok vydání: | 2022 |
| Předmět: |
Male
Mice Knockout General Immunology and Microbiology Serine-Arginine Splicing Factors General Neuroscience Cell Differentiation Cell Cycle Proteins General Medicine General Biochemistry Genetics and Molecular Biology Spermatogonia Repressor Proteins Mice Alternative Splicing Meiosis Animals Humans Spermatogenesis |
| Zdroj: | eLife. 11 |
| ISSN: | 2050-084X |
| Popis: | 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 a germ cell-specific knockout mouse model, we demonstrated that the splicing factor Srsf10 is essential for spermatogenesis and male fertility. In the absence of SRSF10, spermatogonial stem cells can be formed, but the expansion of Promyelocytic Leukemia Zinc Finger (PLZF)-positive undifferentiated progenitors was impaired, followed by the failure of spermatogonia differentiation (marked by KIT expression) 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. Notably, SRSF10 directly binds thousands of genes in isolated THY+ spermatogonia, and Srsf10 depletion disturbed the alternative splicing of genes that are preferentially associated with germ cell development, cell cycle, and chromosome segregation, including Nasp, Bclaf1, Rif1, Dazl, Kit, Ret, and Sycp1. These data suggest that SRSF10 is critical for the expansion of undifferentiated progenitors by regulating alternative splicing, expanding our understanding of the mechanism underlying spermatogenesis. |
| Databáze: | OpenAIRE |
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