Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Cell Rep. 2024 Apr 23;43(4):114113. doi: 10.1016/j.celrep.2024.114113. Epub 2024 Apr 15.
The continuous regeneration of spermatogonial stem cells (SSCs) underpins spermatogenesis and lifelong male fertility, but the developmental origins of the SSC pool remain unclear. Here, we document that hnRNPU is essential for establishing the SSC pool. In male mice, conditional loss of hnRNPU in prospermatogonia (ProSG) arrests spermatogenesis and results in sterility. hnRNPU-deficient ProSG fails to differentiate and migrate to the basement membrane to establish SSC pool in infancy. Moreover, hnRNPU deletion leads to the accumulation of ProSG and disrupts the process of T1-ProSG to T2-ProSG transition. Single-cell transcriptional analyses reveal that germ cells are in a mitotically quiescent state and lose their unique identity upon hnRNPU depletion. We further show that hnRNPU could bind to Vrk1, Slx4, and Dazl transcripts that have been identified to suffer aberrant alternative splicing in hnRNPU-deficient testes. These observations offer important insights into SSC pool establishment and may have translational implications for male fertility.
精原干细胞（SSC）的持续再生是精子发生和男性终身生育能力的基础，但 SSC 池的发育起源仍不清楚。在这里，我们证明 hnRNPU 对于建立 SSC 池是必不可少的。在雄性小鼠中，条件性地在精原前体细胞（ProSG）中缺失 hnRNPU 会阻止精子发生并导致不育。hnRNPU 缺陷的 ProSG 无法分化并迁移到基底膜，从而在婴儿期无法建立 SSC 池。此外，hnRNPU 的缺失导致 ProSG 的积累，并破坏了 T1-ProSG 到 T2-ProSG 过渡的过程。单细胞转录组分析显示，生殖细胞处于有丝分裂静止状态，并在 hnRNPU 耗竭时失去其独特的身份。我们进一步表明，hnRNPU 可以结合到已经在 hnRNPU 缺陷睾丸中发生异常选择性剪接的 Vrk1、Slx4 和 Dazl 转录本上。这些观察结果为 SSC 池的建立提供了重要的见解，并可能对男性生育能力具有转化意义。
