Ascorbic acid enhances differentiation of embryonic stem cells into cardiac myocytes
Ascorbic acid enhances differentiation of embryonic stem cells into cardiac myocytes
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DOI：
10.1161/01.cir.0000064899.53876.a3
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发表时间：
2003-04-15
期刊：
影响因子：
37.8
通讯作者：
Lee, RT
中科院分区：
文献类型：
--
作者：
Takahashi, T;Lord, B;Lee, RT
背景-胚胎干细胞（ES）能够自我更新并分化为所有3个胚层的细胞衍生物。在适当的培养条件下，ES细胞可以分化成专门的细胞，包括心肌细胞，但效率通常是低的，该过程是不完全understood.Methods和Results-We评估了其潜在的化学库诱导心脏分化的ES细胞在没有胚状体形成。使用稳定转染有心脏特异性α-心肌肌球蛋白重链（MHC）启动子驱动的增强型绿色荧光蛋白（EGFP）的ES细胞，筛选了880种批准用于人类的化合物，以确定它们诱导心脏分化的能力。抗坏血酸（也称为维生素C）治疗显著增加了EGFP阳性细胞的数量，这些细胞显示出自发的和有节奏的收缩活动，并对肌节肌球蛋白和α-辅肌动蛋白染色呈阳性。此外，抗坏血酸诱导心脏基因的表达，包括GATA 4，α-MHC，β-MHC在未转染的ES细胞在发育控制的方式。抗坏血酸对心脏分化的这种作用并不被其他抗氧化剂（例如N-乙酰半胱氨酸、Tiron或维生素E）所模仿。结论-抗坏血酸诱导ES细胞的心脏分化。这项研究表明了化学修饰ES细胞的心脏分化程序的潜力。
Background-Embryonic stem (ES) cells are capable of self-renewal and differentiation into cellular derivatives of all 3 germ layers. In appropriate culture conditions, ES cells can differentiate into specialized cells, including cardiac myocytes, but the efficiency is typically low and the process is incompletely understood.Methods and Results-We evaluated a chemical library for its potential to induce cardiac differentiation of ES cells in the absence of embryoid body formation. Using ES cells stably transfected with cardiac-specific alpha-cardiac myosin heavy chain (MHC) promoter-driven enhanced green fluorescent protein (EGFP), 880 compounds approved for human use were screened for their ability to induce cardiac differentiation. Treatment with ascorbic acid, also known as vitamin C, markedly increased the number of EGFP-positive cells, which displayed spontaneous and rhythmic contractile activity and stained positively for sarcomeric myosin and alpha-actinin. Furthermore, ascorbic acid induced the expression of cardiac genes, including GATA4, alpha-MHC, and beta-MHC in untransfected ES cells in a developmentally controlled manner. This effect of ascorbic acid on cardiac differentiation was not mimicked by the other antioxidants such as N-acetylcysteine, Tiron, or vitamin E.Conclusions-Ascorbic acid induces cardiac differentiation in ES cells. This study demonstrates the potential for chemically modifying the cardiac differentiation program of ES cells.