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

Authors

  • Zuping He,

    1. Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, USA
    2. Clinical Stem Cell Research Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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  • Jiji Jiang,

    1. Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, USA
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  • Maria Kokkinaki,

    1. Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, USA
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  • Lin Tang,

    1. Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada
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  • Wenxian Zeng,

    1. Northwest Agricultural and Forest University, Shanxi, China
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  • Ian Gallicano,

    1. Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, USA
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  • Ina Dobrinski,

    1. Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada
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  • Martin Dym

    Corresponding author
    1. Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, USA
    • Correspondence: Martin Dym, Ph.D., Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC 20057, USA. Telephone: 202–687-1184; Fax: 240–778-2843; e-mail: dymm@georgetown.edu,

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  • Author contributions: M.D.: conception and design; financial support; manuscript writing; final approval of manuscript; data analysis and interpretation; I.G.: conception and design; provision of study material (miRNA mimics and inhibitors); other (continuous guidance and discussions); Z.H.: conception and design; collection and assembly of data; manuscript writing; data analysis and interpretation; L.T., W.Z. and I.D.: collection and assembly of data (transplant work); J.J. and M.K.: collection and assembly of data.

Abstract

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. Stem Cells 2013;31:2205–2217

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