Down-regulation of myogenin can reverse terminal muscle cell differentiation.
Down-regulation of myogenin can reverse terminal muscle cell differentiation.
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DOI：
10.1371/journal.pone.0029896
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Phylactou LA
中科院分区：
文献类型：
--
作者：
Mastroyiannopoulos NP;Nicolaou P;Anayasa M;Uney JB;Phylactou LA
某些高等脊椎动物发展了逆转肌肉细胞分化（去分化）的能力，作为再生肌肉的额外机制。另一方面，哺乳动物逆转肌肉细胞分化的能力有限。肌生成调节因子（MRF）、MyoD、肌生成素、Myf5和Myf6是调节肌生成所必需的碱性螺旋环螺旋（bHLH）转录因子。我们目前的兴趣是研究是否在终末分化的小鼠肌管中下调MRF可以诱导肌细胞分化逆转。这项工作的结果表明，降低终末分化小鼠肌管中的肌生成素水平可以逆转其分化状态。终末分化的小鼠肌管中肌细胞生成素的下调诱导细胞分裂成单核细胞和细胞周期重新进入，如DNA合成的重新启动和细胞周期蛋白D1和细胞周期蛋白E2水平增加所示。最后，我们提供的证据表明，肌细胞生成素的下调导致细胞周期重新进入（通过下调MyoD）和细胞化通过不同的途径。这些数据揭示了肌细胞生成素在维持终末肌细胞分化中的重要作用，并指出了一种新的机制，通过这种机制，肌细胞可以通过其下调而重新激活。
Certain higher vertebrates developed the ability to reverse muscle cell differentiation (dedifferentiation) as an additional mechanism to regenerate muscle. Mammals, on the other hand, show limited ability to reverse muscle cell differentiation. Myogenic Regulatory Factors (MRFs), MyoD, myogenin, Myf5 and Myf6 are basic-helix-loop-helix (bHLH) transcription factors essential towards the regulation of myogenesis. Our current interest is to investigate whether down-regulation of MRFs in terminally differentiated mouse myotubes can induce reversal of muscle cell differentiation. Results from this work showed that reduction of myogenin levels in terminally differentiated mouse myotubes can reverse their differentiation state. Down-regulation of myogenin in terminally differentiated mouse myotubes induces cellular cleavage into mononucleated cells and cell cycle re-entry, as shown by re-initiation of DNA synthesis and increased cyclin D1 and cyclin E2 levels. Finally, we provide evidence that down-regulation of myogenin causes cell cycle re-entry (via down-regulation of MyoD) and cellularisation through separate pathways. These data reveal the important role of myogenin in maintaining terminal muscle cell differentiation and point to a novel mechanism by which muscle cells could be re-activated through its down-regulation.
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影响因子：
56.9
作者：
HALEVY, O;NOVITCH, BG;LASSAR, AB
通讯作者：
LASSAR, AB
影响因子：
3.7
作者：
Mu, Xiaodong;Peng, Hairong;Li, Yong
通讯作者：
Li, Yong
DOI：
10.1083/jcb.200509011
发表时间：
2006-01-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Morrison JI;Lööf S;He P;Simon A
通讯作者：
Simon A
影响因子：
10.5
作者：
EDMONDSON, DG;OLSON, EN
通讯作者：
OLSON, EN
影响因子：
64.8
作者：
HASTY, P;BRADLEY, A;KLEIN, WH
通讯作者：
KLEIN, WH