Epigenetic Manipulation Facilitates the Generation of Skeletal Muscle Cells from Pluripotent Stem Cells.
Epigenetic Manipulation Facilitates the Generation of Skeletal Muscle Cells from Pluripotent Stem Cells.
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DOI：
10.1155/2017/7215010
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发表时间：
2017
影响因子：
4.3
通讯作者：
Ko MSH
中科院分区：
文献类型：
--
作者：
Akiyama T;Wakabayashi S;Soma A;Sato S;Nakatake Y;Oda M;Murakami M;Sakota M;Chikazawa-Nohtomi N;Ko SBH;Ko MSH
人类多能干细胞（hPSCs）具有分化为体内所有细胞类型的能力。这种分化可以通过适当的细胞培养条件或过度表达谱系定义转录因子（tf）来定向到特定的细胞类型。特别是对于肌原性程序的激活，早期的研究表明，与肌原性分化相关的tf（如PAX7和MYOD1）的强制表达是有效的。然而，直接分化的效率相当低，很可能是由于hPSCs特有的染色质特征，这阻碍了tf进入参与肌肉分化的基因。事实上，最近的研究表明，表观遗传修饰因子（如组蛋白去甲基化酶和atp依赖性重塑因子）的异位表达显著增强了hPSCs的肌源性分化。在这篇文章中，我们回顾了通过强迫表观遗传和转录操作从hPSCs体外生成骨骼肌的最新进展。
Human pluripotent stem cells (hPSCs) have the capacity to differentiate into essentially all cell types in the body. Such differentiation can be directed to specific cell types by appropriate cell culture conditions or overexpressing lineage-defining transcription factors (TFs). Especially, for the activation of myogenic program, early studies have shown the effectiveness of enforced expression of TFs associated with myogenic differentiation, such as PAX7 and MYOD1. However, the efficiency of direct differentiation was rather low, most likely due to chromatin features unique to hPSCs, which hinder the access of TFs to genes involved in muscle differentiation. Indeed, recent studies have demonstrated that ectopic expression of epigenetic-modifying factors such as a histone demethylase and an ATP-dependent remodeling factor significantly enhances myogenic differentiation from hPSCs. In this article, we review the recent progress for in vitro generation of skeletal muscles from hPSCs through forced epigenetic and transcriptional manipulation.