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MicroRNA-202 maintains spermatogonial stem cells by inhibiting cell cycle regulators and RNA binding proteins
miRNAs play important roles during mammalian spermatogenesis. However, the function of most miRNAs in spermatogenesis and the underlying mechanisms remain unknown. Here, we report that miR-202 is highly expressed in mouse spermatogonial stem cells (SSCs), and is oppositely regulated by Glial cell-De...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5397178/ https://www.ncbi.nlm.nih.gov/pubmed/27998933 http://dx.doi.org/10.1093/nar/gkw1287 |
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author | Chen, Jian Cai, Tanxi Zheng, Chunwei Lin, Xiwen Wang, Guojun Liao, Shangying Wang, Xiuxia Gan, Haiyun Zhang, Daoqin Hu, Xiangjing Wang, Si Li, Zhen Feng, Yanmin Yang, Fuquan Han, Chunsheng |
author_facet | Chen, Jian Cai, Tanxi Zheng, Chunwei Lin, Xiwen Wang, Guojun Liao, Shangying Wang, Xiuxia Gan, Haiyun Zhang, Daoqin Hu, Xiangjing Wang, Si Li, Zhen Feng, Yanmin Yang, Fuquan Han, Chunsheng |
author_sort | Chen, Jian |
collection | PubMed |
description | miRNAs play important roles during mammalian spermatogenesis. However, the function of most miRNAs in spermatogenesis and the underlying mechanisms remain unknown. Here, we report that miR-202 is highly expressed in mouse spermatogonial stem cells (SSCs), and is oppositely regulated by Glial cell-Derived Neurotrophic Factor (GDNF) and retinoic acid (RA), two key factors for SSC self-renewal and differentiation. We used inducible CRISPR-Cas9 to knockout miR-202 in cultured SSCs, and found that the knockout SSCs initiated premature differentiation accompanied by reduced stem cell activity and increased mitosis and apoptosis. Target genes were identified with iTRAQ-based proteomic analysis and RNA sequencing, and are enriched with cell cycle regulators and RNA-binding proteins. Rbfox2 and Cpeb1 were found to be direct targets of miR-202 and Rbfox2 but not Cpeb1, is essential for the differentiation of SSCs into meiotic cells. Accordingly, an SSC fate-regulatory network composed of signaling molecules of GDNF and RA, miR-202 and diverse downstream effectors has been identified. |
format | Online Article Text |
id | pubmed-5397178 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-53971782017-04-24 MicroRNA-202 maintains spermatogonial stem cells by inhibiting cell cycle regulators and RNA binding proteins Chen, Jian Cai, Tanxi Zheng, Chunwei Lin, Xiwen Wang, Guojun Liao, Shangying Wang, Xiuxia Gan, Haiyun Zhang, Daoqin Hu, Xiangjing Wang, Si Li, Zhen Feng, Yanmin Yang, Fuquan Han, Chunsheng Nucleic Acids Res RNA miRNAs play important roles during mammalian spermatogenesis. However, the function of most miRNAs in spermatogenesis and the underlying mechanisms remain unknown. Here, we report that miR-202 is highly expressed in mouse spermatogonial stem cells (SSCs), and is oppositely regulated by Glial cell-Derived Neurotrophic Factor (GDNF) and retinoic acid (RA), two key factors for SSC self-renewal and differentiation. We used inducible CRISPR-Cas9 to knockout miR-202 in cultured SSCs, and found that the knockout SSCs initiated premature differentiation accompanied by reduced stem cell activity and increased mitosis and apoptosis. Target genes were identified with iTRAQ-based proteomic analysis and RNA sequencing, and are enriched with cell cycle regulators and RNA-binding proteins. Rbfox2 and Cpeb1 were found to be direct targets of miR-202 and Rbfox2 but not Cpeb1, is essential for the differentiation of SSCs into meiotic cells. Accordingly, an SSC fate-regulatory network composed of signaling molecules of GDNF and RA, miR-202 and diverse downstream effectors has been identified. Oxford University Press 2017-04-20 2016-12-20 /pmc/articles/PMC5397178/ /pubmed/27998933 http://dx.doi.org/10.1093/nar/gkw1287 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | RNA Chen, Jian Cai, Tanxi Zheng, Chunwei Lin, Xiwen Wang, Guojun Liao, Shangying Wang, Xiuxia Gan, Haiyun Zhang, Daoqin Hu, Xiangjing Wang, Si Li, Zhen Feng, Yanmin Yang, Fuquan Han, Chunsheng MicroRNA-202 maintains spermatogonial stem cells by inhibiting cell cycle regulators and RNA binding proteins |
title | MicroRNA-202 maintains spermatogonial stem cells by inhibiting cell cycle regulators and RNA binding proteins |
title_full | MicroRNA-202 maintains spermatogonial stem cells by inhibiting cell cycle regulators and RNA binding proteins |
title_fullStr | MicroRNA-202 maintains spermatogonial stem cells by inhibiting cell cycle regulators and RNA binding proteins |
title_full_unstemmed | MicroRNA-202 maintains spermatogonial stem cells by inhibiting cell cycle regulators and RNA binding proteins |
title_short | MicroRNA-202 maintains spermatogonial stem cells by inhibiting cell cycle regulators and RNA binding proteins |
title_sort | microrna-202 maintains spermatogonial stem cells by inhibiting cell cycle regulators and rna binding proteins |
topic | RNA |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5397178/ https://www.ncbi.nlm.nih.gov/pubmed/27998933 http://dx.doi.org/10.1093/nar/gkw1287 |
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