microRNA-1 and microRNA-206 regulate skeletal muscle satellite cell proliferation and differentiation by repressing Pax7.
microRNA-1 and microRNA-206 regulate skeletal muscle satellite cell proliferation and differentiation by repressing Pax7.
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DOI：
10.1083/jcb.200911036
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发表时间：
2010-09-06
期刊：
影响因子：
--
通讯作者：
Wang DZ
中科院分区：
文献类型：
--
作者：
Chen JF;Tao Y;Li J;Deng Z;Yan Z;Xiao X;Wang DZ
Pax 7是两种miRNAs的靶点，这两种miRNAs在肌肉卫星细胞分化过程中被诱导，并在肌肉损伤时被抑制。骨骼肌卫星细胞是负责出生后骨骼肌生长和再生的成体干细胞。Pax 7在卫星细胞存活、自我更新和增殖中起着重要作用。然而，在从增殖卫星细胞向分化肌源性祖细胞的过渡过程中，Pax 7是如何调节的在很大程度上是未知的。在这项研究中，我们发现miR-1和miR-206在卫星细胞分化过程中急剧上调，在肌肉损伤后下调。我们发现miR-1和miR-206通过限制其增殖潜力促进卫星细胞分化。我们确定Pax 7是miR-1和miR-206的直接调控靶点之一。抑制miR-1和miR-206显著增强卫星细胞增殖并增加体内Pax 7蛋白水平。相反，由于miR-1和miR-206抑制元件在其3′非翻译区的缺失，Pax 7的持续表达显著抑制成肌细胞分化。因此，我们的实验表明，microRNA参与了一个调控回路，允许快速的基因程序从增殖到分化的转变。
Pax7 is a target of two miRNAs that are induced during muscle satellite cell differentiation and repressed in response to muscle injury. Skeletal muscle satellite cells are adult stem cells responsible for postnatal skeletal muscle growth and regeneration. Paired-box transcription factor Pax7 plays a central role in satellite cell survival, self-renewal, and proliferation. However, how Pax7 is regulated during the transition from proliferating satellite cells to differentiating myogenic progenitor cells is largely unknown. In this study, we find that miR-1 and miR-206 are sharply up-regulated during satellite cell differentiation and down-regulated after muscle injury. We show that miR-1 and miR-206 facilitate satellite cell differentiation by restricting their proliferative potential. We identify Pax7 as one of the direct regulatory targets of miR-1 and miR-206. Inhibition of miR-1 and miR-206 substantially enhances satellite cell proliferation and increases Pax7 protein level in vivo. Conversely, sustained Pax7 expression as a result of the loss of miR-1 and miR-206 repression elements at its 3′ untranslated region significantly inhibits myoblast differentiation. Therefore, our experiments suggest that microRNAs participate in a regulatory circuit that allows rapid gene program transitions from proliferation to differentiation.
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DOI：
10.1083/jcb.200508001
发表时间：
2006-01-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kuang S;Chargé SB;Seale P;Huh M;Rudnicki MA
通讯作者：
Rudnicki MA
DOI：
10.1083/jcb.200603008
发表时间：
2006-08-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kim HK;Lee YS;Sivaprasad U;Malhotra A;Dutta A
通讯作者：
Dutta A
影响因子：
2.7
作者：
Olguin, HC;Olwin, BB
通讯作者：
Olwin, BB
影响因子：
14.9
作者：
Griffiths-Jones, S
通讯作者：
Griffiths-Jones, S
影响因子：
11.8
作者：
Conboy, IM;Rando, TA
通讯作者：
Rando, TA