PDF(Pubmed)
Abstract：
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.
摘要：
精原干细胞（SSC）对于持续的精子发生和男性生育能力至关重要。小鼠SSC中选择性剪接（AS）的潜在机制仍不清楚。我们证明了SRSF1对于小鼠SSC中的基因表达和剪接至关重要。交联免疫沉淀和测序数据显示，精原细胞相关基因（例如Plzf，Id4,Setdb1,Stra8,Tial1/Tiar,Bcas2，Ddx5，Srsf10，Uhrf1和Bud31）在小鼠睾丸中被SRSF1结合。小鼠生殖细胞中Srsf1的特异性缺失会损害前体SSC的归巢，导致男性不育。整装染色数据显示成年条件敲除（cKO）小鼠睾丸中不存在生殖细胞，这表明cKO小鼠中的仅支持细胞综合征。精原细胞相关基因的表达（例如Gfra1，Pou5f1，Plzf，在cKO小鼠的睾丸中Dnd1，Stra8和Taf4b）显着降低。此外，多组学分析表明，SRSF1可能通过AS直接结合和调节Tial1/Tiar的表达来影响精原细胞的存活。此外,免疫沉淀质谱和共免疫沉淀数据显示SRSF1与RNA剪接相关蛋白(例如SART1、RBM15和SRSF10)相互作用。总的来说，我们的数据揭示了SRSF1在精原细胞存活中的关键作用，这可能提供一个框架来阐明前体SSC归巢的转录后网络的分子机制。
