hnRNPU is required for spermatogonial stem cell pool establishment in mice
Yujiao Wen,
Shumin Zhou,
Yiqian Gui,
Zeqing Li,
Lisha Yin,
Wenchao Xu,
Shenglei Feng,
Xixiang Ma,
Shiming Gan,
Mengneng Xiong,
Juan Dong,
Keren Cheng,
Xiaoli Wang,
Shuiqiao Yuan
Affiliations
Yujiao Wen
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
Shumin Zhou
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Yiqian Gui
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Zeqing Li
School of Nuclear Technology and Chemistry & Biology, Hubei University of Science and Technology, Xianning 437100, China
Lisha Yin
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Wenchao Xu
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Shenglei Feng
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Laboratory of Animal Center, Huazhong University of Science and Technology, Wuhan 430030, China
Xixiang Ma
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Laboratory of Animal Center, Huazhong University of Science and Technology, Wuhan 430030, China
Shiming Gan
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Mengneng Xiong
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Juan Dong
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Keren Cheng
Center for Reproductive Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, China
Xiaoli Wang
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Shuiqiao Yuan
Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Laboratory of Animal Center, Huazhong University of Science and Technology, Wuhan 430030, China; Shenzhen Huazhong University of Science and Technology Research Institute, Shenzhen 518057, China; Corresponding author
Summary: 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.
