Splicing factor SRSF1 is essential for homing of precursor spermatogonial stem cells in mice

• Published in: eLife Vol. 12
• Main Authors: Sun, Longjie, Lv, Zheng, Chen, Xuexue, Ye, Rong, Tian, Shuang, Wang, Chaofan, Xie, Xiaomei, Yan, Lu, Yao, Xiaohong, Shao, Yujing, Cui, Sheng, Chen, Juan, Liu, Jiali
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 25.01.2024; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Alternative splicing; Analysis; Antibodies; Cell Biology; Developmental Biology; Fertility; Gene expression; Genes; Genomics; Germ cells; homing of precursor SSCs; Immunoprecipitation; Infertility; Localization; Mass spectroscopy; Molecular modelling; Oct-4 protein; Ontology; Post-transcription; precursor spermatogonial stem cells; Proteins; RNA; Sertoli cell-only syndrome; Sperm; Spermatogenesis; Spermatogonia; Splicing factors; SRSF1; Stem cells; Testes; mouse; cell biology; alternative splicing; precursor spermatogonial stem cells; developmental biology; SRSF1; homing of precursor SSCs; infertility; Sertoli cell-only syndrome
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.89316

Spermatogonial stem cells (SSCs) are essential for continuous spermatogenesis and male fertility. The underlying mechanisms of alternative splicing (AS) in mouse SSCs are still largely unclear. We demonstrated that SRSF1 is essential for gene expression and splicing in mouse SSCs. Crosslinking immunoprecipitation and sequencing data revealed that spermatogonia-related genes (e.g. , , , / , , , , , and ) were bound by SRSF1 in the mouse testes. Specific deletion of in mouse germ cells impairs homing of precursor SSCs leading to male infertility. Whole-mount staining data showed the absence of germ cells in the testes of adult conditional knockout (cKO) mice, which indicates Sertoli cell-only syndrome in cKO mice. The expression of spermatogonia-related genes (e.g. , , , , , and ) was significantly reduced in the testes of cKO mice. Moreover, multiomics analysis suggests that SRSF1 may affect survival of spermatogonia by directly binding and regulating / expression through AS. In addition, immunoprecipitation mass spectrometry and co-immunoprecipitation data showed that SRSF1 interacts with RNA splicing-related proteins (e.g. SART1, RBM15, and SRSF10). Collectively, our data reveal the critical role of SRSF1 in spermatogonia survival, which may provide a framework to elucidate the molecular mechanisms of the posttranscriptional network underlying homing of precursor SSCs.