The homeobox transcription factor Barx2 regulates plasticity of young primary myofibers.
The homeobox transcription factor Barx2 regulates plasticity of young primary myofibers.
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DOI：
10.1371/journal.pone.0011612
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发表时间：
2010-07-15
期刊：
影响因子：
3.7
通讯作者：
Makarenkova HP
中科院分区：
文献类型：
--
作者：
Meech R;Gomez M;Woolley C;Barro M;Hulin JA;Walcott EC;Delgado J;Makarenkova HP
成年哺乳动物的肌肉保持着不可思议的可塑性。肌肉的生长和修复涉及被称为卫星细胞的未分化的肌源性前体的激活。在某些情况下，已经存在的肌纤维也可能分裂并产生增殖细胞池，这些细胞可以重新分化成新的纤维。这种肌纤维去分化已经在蝾螈胚中被观察到，它可能与卫星细胞激活同时发生。此外，同源结构域转录因子Msx1在分化的C2C12肌管中的异位表达已被证明可诱导其去分化。虽然目前尚不清楚去分化和再分化是否发生在哺乳动物肌肉中，但诱导去分化作为一种可能的再生工具已经引起了相当大的兴趣。我们之前发现同源盒蛋白Barx2促进成肌细胞分化。在这里，我们报道了Barx2在来自细胞系和原代小鼠成肌细胞的年轻未成熟肌管中的异位表达，导致合胞体的分裂和分化标记的下调。将Barx2 cDNA微注射到原代细胞衍生的未成熟肌管中，导致分裂并形成能够增殖的单核细胞。然而，将Barx2 cDNA注射到成熟的肌管中不会引起分裂。Barx2在C2C12肌管中的表达增加了cyclin D1的表达，可能促进了细胞周期的再进入。我们还观察到Barx2在肌肉分化的早期和晚期对肌肉基因的不同调控，这可能是由于Barx2对肌肉特定基因的转录激活因子或抑制因子复合物的不同募集。我们发现Barx2调节未成熟肌纤维的可塑性，并可能作为控制细胞分化和增殖的分子开关。
Adult mammalian muscle retains incredible plasticity. Muscle growth and repair involves the activation of undifferentiated myogenic precursors called satellite cells. In some circumstances, it has been proposed that existing myofibers may also cleave and produce a pool of proliferative cells that can re-differentiate into new fibers. Such myofiber dedifferentiation has been observed in the salamander blastema where it may occur in parallel with satellite cell activation. Moreover, ectopic expression of the homeodomain transcription factor Msx1 in differentiated C2C12 myotubes has been shown to induce their dedifferentiation. While it remains unclear whether dedifferentiation and redifferentiaton occurs endogenously in mammalian muscle, there is considerable interest in induced dedifferentiation as a possible regenerative tool. We previously showed that the homeobox protein Barx2 promotes myoblast differentiation. Here we report that ectopic expression of Barx2 in young immature myotubes derived from cell lines and primary mouse myoblasts, caused cleavage of the syncytium and downregulation of differentiation markers. Microinjection of Barx2 cDNA into immature myotubes derived from primary cells led to cleavage and formation of mononucleated cells that were able to proliferate. However, injection of Barx2 cDNA into mature myotubes did not cause cleavage. Barx2 expression in C2C12 myotubes increased the expression of cyclin D1, which may promote cell cycle re-entry. We also observed differential muscle gene regulation by Barx2 at early and late stages of muscle differentiation which may be due to differential recruitment of transcriptional activator or repressor complexes to muscle specific genes by Barx2. We show that Barx2 regulates plasticity of immature myofibers and might act as a molecular switch controlling cell differentiation and proliferation.
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影响因子：
10.5
作者：
LaBaer, J;Garrett, MD;Harlow, E
通讯作者：
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影响因子：
2.9
作者：
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DOI：
10.1098/rspb.1995.0024
发表时间：
1995-02-22
影响因子：
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作者：
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通讯作者：
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影响因子：
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