Twist induces reversal of myotube formation
Twist induces reversal of myotube formation
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DOI：
10.1111/j.1432-0436.2007.00195.x
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发表时间：
2008-02-01
期刊：
影响因子：
2.9
通讯作者：
Phylactou, Leonidas A.
中科院分区：
文献类型：
--
作者：
Hjiantoniou, Eleni;Anayasa, Mustafa;Phylactou, Leonidas A.
与其他脊椎动物相比，哺乳动物再生丢失组织的能力较弱，其他脊椎动物可以通过前体细胞的分化或去分化来再生。哺乳动物多核肌管的形成是一种分化过程，它起源于单核成肌细胞的融合，被认为是一个不可逆转的肌肉形成过程。通过在末端分化的肌管中过表达Twist基因，我们成功地诱导了细胞分化的逆转。更具体地说，在Twist基因表达之后，肌管经历了导致它们分裂的形态变化。伴随而来的是某些肌源性标志物的表达减少。有趣的是，Twist的过度表达也导致了肌肉转录因子MyoD的减少。进一步的实验表明，由于Twist的过度表达，细胞周期进入分子Cyclin D1和DNA合成的启动增加。利用Twist介导的分化逆转及其特定机制的研究对于研究哺乳动物细胞的去分化和确定其在肌肉再生中的潜力具有重要意义。
Mammals possess reduced ability to regenerate lost tissue, compared with other vertebrates, which can regenerate through differentiation of precursor cells or de-differentiation. Mammalian multinucleated myotube formation is a differentiation process, which arises from the fusion of mononucleated myoblasts and is thought to be an irreversible process toward muscle formation. By overexpressing the Twist gene in terminally differentiated myotubes, we managed to induce reversal of cell differentiation. More specifically, following expression of the Twist gene, myotubes underwent morphological changes that caused them to cleave. This was accompanied by a reduction in the expression of certain myogenic markers. Interestingly, Twist overexpression also caused a reduction in the muscle transcription factor MyoD. Further experiments showed an increase in the cell cycle entry molecule, cyclin D1 and initiation of DNA synthesis, due to Twist overexpression. The exploitation of Twist-mediated reversal of differentiation and the study of its specific mechanism would be important in order to study mammalian cellular de-differentiation and determine its potential in muscle regeneration.