TY - JOUR
T1 - MicroRNA-21 regulates the self-renewal of mouse spermatogonial stem cells
AU - Niu, Zhiyv
AU - Goodyear, Shaun M.
AU - Rao, Shilpa
AU - Wu, Xin
AU - Tobias, John W.
AU - Avarbock, Mary R.
AU - Brinster, Ralph L.
PY - 2011/8/2
Y1 - 2011/8/2
N2 - 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.
AB - 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.
KW - Male germline stem cells
KW - Small RNA
UR - http://www.scopus.com/inward/record.url?scp=79961219742&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79961219742&partnerID=8YFLogxK
U2 - 10.1073/pnas.1109987108
DO - 10.1073/pnas.1109987108
M3 - Article
C2 - 21768389
AN - SCOPUS:79961219742
SN - 0027-8424
VL - 108
SP - 12740
EP - 12745
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 31
ER -