title: MicroRNA-21 regulates the self-renewal of mouse spermatogonial stem cells.
abstract: MicroRNAs (miRs) play a key role in the control of gene expression in a wide array of tissue systems, where their functions include the regulation of self-renewal, cellular differentiation, proliferation, and apoptosis. However, the functional importance of individual miRs in controlling spermatogonial stem cell (SSC) homeostasis has not been investigated. Using high-throughput sequencing, we profiled the expression of miRs in the Thy1(+) testis cell population, which is highly enriched for SSCs, and the Thy1(-) cell population, composed primarily of testis somatic cells. In addition, we profiled the global expression of miRs in cultured germ cells, also enriched for SSCs. Our results demonstrate that miR-21, along with miR-34c, -182, -183, and -146a, are preferentially expressed in the Thy1(+) SSC-enriched population, compared with Thy1(-) somatic cells. Importantly, we demonstrate that transient inhibition of miR-21 in SSC-enriched germ cell cultures increased the number of germ cells undergoing apoptosis and significantly reduced the number of donor-derived colonies of spermatogenesis formed from transplanted treated cells in recipient mouse testes, indicating that miR-21 is important in maintaining the SSC population. Moreover, we show that in SSC-enriched germ cell cultures, miR-21 is regulated by the transcription factor ETV5, known to be critical for SSC self-renewal.
authors.affiliation: Department of Animal Biology, School of Veterinary Medicine, and Penn Bioinformatics Core, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Zhiyv
authors.initials: Z
authors.lastname: Niu
authors.forename: Shaun M
authors.initials: SM
authors.lastname: Goodyear
authors.forename: Shilpa
authors.initials: S
authors.lastname: Rao
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.forename: John W
authors.initials: JW
authors.lastname: Tobias
authors.forename: Mary R
authors.initials: MR
authors.lastname: Avarbock
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Brinster
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015723:Gene Library; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013091:Spermatogenesis / Q000235:genetics; D013093:Spermatogonia / Q000166:cytology* / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000378:metabolism; D018800:Thy-1 Antigens / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C513242:Etv5 protein, mouse; C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D018800:Thy-1 Antigens; D014157:Transcription Factors