MyoD gene suppression by Oct4 is required for reprogramming in myoblasts to produce induced pluripotent stem cells.
MyoD gene suppression by Oct4 is required for reprogramming in myoblasts to produce induced pluripotent stem cells.
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DOI：
10.1002/stem.598
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发表时间：
2011-03
期刊：
影响因子：
5.2
通讯作者：
Asakura, Atsushi
中科院分区：
文献类型：
--
作者：
Watanabe, Shuichi;Hirai, Hiroyuki;Asakura, Yoko;Tastad, Christopher;Verma, Mayank;Keller, Charles;Dutton, James R.;Asakura, Atsushi
四种转录因子，即Oct 4、Sox 2、cMyc和Klf 4的表达已经显示出从许多类型的特化分化的体细胞产生诱导多能干细胞（iPSC）。然而，目前尚不清楚完全定型的骨骼肌祖细胞（成肌细胞）是否具有与先前报道的病例一致的重新编程以发育iPSC的潜力。为了测试这一点，我们使用Cre-loxP系统（Pax 7-CreER：R26 R和Myf 5-Cre：R26 R）分离了源自成年小鼠肌肉的卫星细胞的遗传标记的成肌细胞。在感染表达这四种因子的逆转录病毒载体后，这些成肌细胞产生了肌源性谱系示踪剂lacZ阳性胚胎干细胞（ESC）样集落。这些细胞表达ESC特异性基因，并且能够分化成所有三个胚层和生殖细胞，表明成肌细胞衍生的iPSC的成功产生。MyoD基因的连续表达，骨骼肌规范的主转录因子，抑制成肌细胞的重编程过程。相反，从缺乏MyoD基因的小鼠中分离的成肌细胞的重编程导致重编程效率的增加。我们的数据还表明，Oct 4通过与上游增强子区域的相互作用作为MyoD基因表达的转录抑制因子。总之，这些结果表明，Oct 4对MyoD基因表达的抑制是从成肌细胞发育iPSC的初始重编程步骤所必需的。这些数据表明，骨骼肌系统提供了一个明确的分化模型，以进一步阐述iPSC重编程在体细胞中的作用。
Expression of the four transcription factors, that is, Oct4, Sox2, cMyc, and Klf4 has been shown to generate induced pluripotent stem cells (iPSCs) from many types of specialized differentiated somatic cells. It remains unclear, however, whether fully committed skeletal muscle progenitor cells (myoblasts) have the potency to undergo reprogramming to develop iPSCs in line with previously reported cases. To test this, we have isolated genetically marked myoblasts derived from satellite cell of adult mouse muscles using the Cre-loxP system (Pax7-CreER:R26R and Myf5-Cre:R26R). On infection with retroviral vectors expressing the four factors, these myoblasts gave rise to myogenic lineage tracer lacZ-positive embryonic stem cell (ESC)-like colonies. These cells expressed ESC-specific genes and were competent to differentiate into all three germ layers and germ cells, indicating the successful generation of myoblast-derived iPSCs. Continuous expression of the MyoD gene, a master transcription factor for skeletal muscle specification, inhibited this reprogramming process in myoblasts. In contrast, reprogramming myoblasts isolated from mice lacking the MyoD gene led to an increase in reprogramming efficiency. Our data also indicated that Oct4 acts as a transcriptional suppressor of MyoD gene expression through its interaction with the upstream enhancer region. Taken together, these results indicate that suppression of MyoD gene expression by Oct4 is required for the initial reprogramming step in the development of iPSCs from myoblasts. This data suggests that the skeletal muscle system provides a well-defined differentiation model to further elaborate on the effects of iPSC reprogramming in somatic cells.
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影响因子：
7.8
作者：
Asakura, Atsushi;Seale, Patrick;Girgis-Gabardo, Adele;Rudnicki, Michael A
通讯作者：
Rudnicki, Michael A
影响因子：
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通讯作者：
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影响因子：
2.9
作者：
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通讯作者：
Rudnicki, MA
影响因子：
56.9
作者：
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通讯作者：
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