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

MiRNA-20 and mirna-106a regulate spermatogonial stem cell renewal at the post-transcriptional level via targeting STAT3 and Ccnd1.
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MiRNA-20 和 MiRNA-106a 通过靶向 STAT3 和 Ccnd1 在转录后水平调节精原干细胞更新

DOI:
10.1002/stem.1474
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发表时间:
2013-10
期刊:
影响因子:
5.2
通讯作者:
Dym, Martin
Dym, Martin
中科院分区:
医学2区
文献类型:
--
作者:
He, Zuping;Jiang, Jiji;Kokkinaki, Maria;Tang, Lin;Zeng, Wenxian;Gallicano, Ian;Dobrinski, Ina;Dym, Martin

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精原干细胞(SSCs)的研究具有不同寻常的意义,因为它们是将遗传信息传递给后代的独特干细胞,并且可以获得多能性,成为胚胎干细胞样细胞,在人类疾病中具有治疗应用。microRNA(miRNAs)是近年来发现的一种重要的哺乳动物细胞内源性调控因子。然而,单个miRNAs在调节SSC命运中的功能和机制仍然未知。在此,我们首次报道了miRNA-20和miRNA-106 a在小鼠精原干细胞中优先表达。使用miRNA模拟物和抑制剂的体外和体内功能测定揭示了miRNA-20和miRNA-106 a对于SSC的更新是必需的。我们进一步证明,这两种miRNA通过靶向STAT 3和Ccnd 1在转录后水平促进更新,并且STAT 3、Fos和Ccnd 1的敲低导致SSC的更新。因此,这项研究提供了新的见解,调节更新和分化的精原干细胞的分子机制,并可能有重要的意义,调节男性生殖。
Studies onspermatogonial 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.
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发表时间: 2001-10-26
期刊: SCIENCE
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