Splicing factor SRSF1 is essential for homing of precursor spermatogonial stem cells in mice.
Longjie SunZheng LvXuexue ChenRong YeShuang TianChaofan WangXiaomei XieLu YanXiaohong YaoYujing ShaoSheng CuiJuan ChenJiali LiuPublished in: eLife (2024)
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. Plzf , Id4 , Setdb1, Stra8 , Tial1 / Tiar , Bcas2 , Ddx5 , Srsf10 , Uhrf1 , and Bud31 ) were bound by SRSF1 in the mouse testes. Specific deletion of Srsf1 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. Gfra1 , Pou5f1 , Plzf , Dnd1 , Stra8 , and Taf4b ) 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 Tial1 / Tiar 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.
Keyphrases
- stem cells
- gene expression
- electronic health record
- high fat diet induced
- single cell
- induced apoptosis
- mass spectrometry
- poor prognosis
- big data
- binding protein
- cell cycle arrest
- cell therapy
- dna methylation
- mesenchymal stem cells
- data analysis
- genome wide
- cell proliferation
- long non coding rna
- adipose tissue
- metabolic syndrome
- free survival
- case report
- skeletal muscle
- transcription factor
- dna binding
- high performance liquid chromatography
- high throughput sequencing
- simultaneous determination