MicroRNA-202 maintains spermatogonial stem cells by inhibiting cell cycle regulators and RNA binding proteins
| Autor: | Xiwen Lin, Yanmin Feng, Si Wang, Shangying Liao, Xiuxia Wang, Zhen Li, Jian Chen, Guojun Wang, Chunwei Zheng, Daoqin Zhang, Haiyun Gan, Fuquan Yang, Tanxi Cai, Xiangjing Hu, Chunsheng Han |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Proteomics Cell signaling RNA-binding protein 03 medical and health sciences Gene Knockout Techniques Neurotrophic factors microRNA Genetics Glial cell line-derived neurotrophic factor Animals Spermatogenesis Mitosis mRNA Cleavage and Polyadenylation Factors biology Adult Germline Stem Cells Sequence Analysis RNA Cell Cycle Cell cycle Cell biology Mice Inbred C57BL Meiosis MicroRNAs 030104 developmental biology Mice Inbred DBA biology.protein RNA RNA Splicing Factors Stem cell Transcription Factors |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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