He Zuping, Jiang Jiji, Kokkinaki Maria, Tang Lin, Zeng Wenxian, Gallicano Ian, Dobrinski Ina, Dym Martin
Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, USA; Clinical Stem Cell Research Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Stem Cells. 2013 Oct;31(10):2205-17. doi: 10.1002/stem.1474.
Studies on spermatogonial stem cells (SSCs) are of unusual significance because they are the unique stem cells that transmit genetic information to subsequent generations and they can acquire pluripotency to become embryonic stem-like cells that have therapeutic applications in human diseases. MicroRNAs (miRNAs) have recently emerged as critical endogenous regulators in mammalian cells. However, the function and mechanisms of individual miRNAs in regulating SSC fate remain unknown. Here, we report for the first time that miRNA-20 and miRNA-106a are preferentially expressed in mouse SSCs. Functional assays in vitro and in vivo using miRNA mimics and inhibitors reveal that miRNA-20 and miRNA-106a are essential for renewal of SSCs. We further demonstrate that these two miRNAs promote renewal at the post-transcriptional level via targeting STAT3 and Ccnd1 and that knockdown of STAT3, Fos, and Ccnd1 results in renewal of SSCs. This study thus provides novel insights into molecular mechanisms regulating renewal and differentiation of SSCs and may have important implications for regulating male reproduction.
对精原干细胞（SSCs）的研究具有特殊意义，因为它们是将遗传信息传递给后代的独特干细胞，并且能够获得多能性，成为在人类疾病治疗中具有应用价值的胚胎干细胞样细胞。微小RNA（miRNAs）最近已成为哺乳动物细胞中的关键内源性调节因子。然而，单个miRNA在调节SSC命运中的功能和机制仍不清楚。在此，我们首次报道miRNA-20和miRNA-106a在小鼠SSCs中优先表达。使用miRNA模拟物和抑制剂进行的体外和体内功能分析表明，miRNA-20和miRNA-106a对SSCs的自我更新至关重要。我们进一步证明，这两种miRNA通过靶向STAT3和Ccnd1在转录后水平促进自我更新，并且敲低STAT3、Fos和Ccnd1会导致SSCs的自我更新。因此，本研究为调节SSCs自我更新和分化的分子机制提供了新的见解，可能对调节雄性生殖具有重要意义。
