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A bstract   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. S tem  C ells   2013;31:2205–2217

MiRNA‐20 and mirna‐106a regulate spermatogonial stem cell renewal at the post‐transcriptional level via targeting STAT3 and Ccnd1