MicroRNA-21 regulates the self-renewal of mouse spermatogonial stem cells

Zhiyv Niu, Shaun M. Goodyear, Shilpa Rao, Xin Wu, John W. Tobias, Mary R. Avarbock, Ralph L. Brinster

Research output: Contribution to journalArticle

169 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)12740-12745
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number31
DOIs
StatePublished - Aug 2 2011

Keywords

  • Male germline stem cells
  • Small RNA

ASJC Scopus subject areas

  • General

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