Splicing factor SRSF1 is essential for homing of precursor spermatogonial stem cells in mice
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 immun...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2024-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/89316 |
| _version_ | 1797346399032967168 |
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| author | Longjie Sun Zheng Lv Xuexue Chen Rong Ye Shuang Tian Chaofan Wang Xiaomei Xie Lu Yan Xiaohong Yao Yujing Shao Sheng Cui Juan Chen Jiali Liu |
| author_facet | Longjie Sun Zheng Lv Xuexue Chen Rong Ye Shuang Tian Chaofan Wang Xiaomei Xie Lu Yan Xiaohong Yao Yujing Shao Sheng Cui Juan Chen Jiali Liu |
| author_sort | Longjie Sun |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T11:32:54Z |
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| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-08T11:32:54Z |
| publishDate | 2024-01-01 |
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| series | eLife |
| spelling | doaj.art-ea00d97583974fcca3b6cdc28c0f63b42024-01-25T17:56:12ZengeLife Sciences Publications LtdeLife2050-084X2024-01-011210.7554/eLife.89316Splicing factor SRSF1 is essential for homing of precursor spermatogonial stem cells in miceLongjie Sun0https://orcid.org/0000-0002-1285-3823Zheng Lv1Xuexue Chen2Rong Ye3Shuang Tian4Chaofan Wang5Xiaomei Xie6Lu Yan7Xiaohong Yao8Yujing Shao9Sheng Cui10https://orcid.org/0000-0002-3826-3768Juan Chen11Jiali Liu12https://orcid.org/0000-0002-6214-569XState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaKey Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaCollege of Veterinary Medicine, Yangzhou University, Jiangsu, ChinaKey Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China, Agricultural University, Beijing, ChinaState Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, ChinaSpermatogonial 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.https://elifesciences.org/articles/89316SRSF1alternative splicingSertoli cell-only syndromeinfertilityprecursor spermatogonial stem cellshoming of precursor SSCs |
| spellingShingle | Longjie Sun Zheng Lv Xuexue Chen Rong Ye Shuang Tian Chaofan Wang Xiaomei Xie Lu Yan Xiaohong Yao Yujing Shao Sheng Cui Juan Chen Jiali Liu Splicing factor SRSF1 is essential for homing of precursor spermatogonial stem cells in mice eLife SRSF1 alternative splicing Sertoli cell-only syndrome infertility precursor spermatogonial stem cells homing of precursor SSCs |
| title | Splicing factor SRSF1 is essential for homing of precursor spermatogonial stem cells in mice |
| title_full | Splicing factor SRSF1 is essential for homing of precursor spermatogonial stem cells in mice |
| title_fullStr | Splicing factor SRSF1 is essential for homing of precursor spermatogonial stem cells in mice |
| title_full_unstemmed | Splicing factor SRSF1 is essential for homing of precursor spermatogonial stem cells in mice |
| title_short | Splicing factor SRSF1 is essential for homing of precursor spermatogonial stem cells in mice |
| title_sort | splicing factor srsf1 is essential for homing of precursor spermatogonial stem cells in mice |
| topic | SRSF1 alternative splicing Sertoli cell-only syndrome infertility precursor spermatogonial stem cells homing of precursor SSCs |
| url | https://elifesciences.org/articles/89316 |
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