Dataset Information


MicroRNA-202 maintains spermatogonial stem cells by inhibiting cell cycle regulators and RNA binding proteins.

ABSTRACT: 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.

PROVIDER: S-EPMC5397178 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC4375941 | BioStudies
| S-EPMC4083858 | BioStudies
| S-EPMC5868990 | BioStudies
| S-EPMC5101510 | BioStudies
| S-EPMC3093986 | BioStudies
2018-01-01 | S-EPMC6197186 | BioStudies
| S-EPMC3810131 | BioStudies
| S-EPMC4983063 | BioStudies
| S-EPMC5830974 | BioStudies
| S-EPMC4823932 | BioStudies