Accelerated direct reprogramming of fibroblasts into cardiomyocyte-like cells with the MyoD transactivation domain
Accelerated direct reprogramming of fibroblasts into cardiomyocyte-like cells with the MyoD transactivation domain
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DOI：
10.1093/cvr/cvt167
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发表时间：
2013-10-01
影响因子：
10.8
通讯作者：
Kikyo, Nobuaki
中科院分区：
文献类型：
--
作者：
Hirai, Hiroyuki;Katoku-Kikyo, Nobuko;Kikyo, Nobuaki
成纤维细胞可以通过引入特定基因直接重编程为心肌样细胞。然而，重编程效率仍然很低，延迟了该策略在再生心脏病学中的临床应用。我们先前表明，MyoD反式激活结构域与多能性转录因子Oct4的融合促进了Oct4的转录活性，导致诱导多能干细胞的高效产生。我们研究了同样的方法是否可以应用于心脏转录因子，以促进心脏reprogramming.We融合MyoD结构域Mef2c，Gata4，Hand2，和Tbx5和转导这些基因在不同的组合到小鼠非心脏成纤维细胞。转导嵌合Mef2c与野生型的其他三个基因产生更大的跳动群集的心肌细胞样细胞的速度比四个野生型基因的组合，与3.5，15倍以上的效率比野生型genes.Fusion的一个强大的反式激活结构域异源因子可以增加直接重编程成纤维细胞的心肌细胞的效率。
Fibroblasts can be directly reprogrammed to cardiomyocyte-like cells by introducing defined genes. However, the reprogramming efficiency remains low, delaying the clinical application of this strategy to regenerative cardiology. We previously showed that fusion of the MyoD transactivation domain to the pluripotency transcription factor Oct4 facilitated the transcriptional activity of Oct4, resulting in highly efficient production of induced pluripotent stem cells. We examined whether the same approach can be applied to cardiac transcription factors to facilitate cardiac reprogramming.We fused the MyoD domain to Mef2c, Gata4, Hand2, and Tbx5 and transduced these genes in various combinations into mouse non-cardiac fibroblasts. Transduction of the chimeric Mef2c with the wild-types of the other three genes produced much larger beating clusters of cardiomyocyte-like cells faster than the combination of the four wild-type genes, with an efficiency of 3.5, 15-fold greater than the wild-type genes.Fusion of a powerful transactivation domain to heterologous factors can increase the efficiency of direct reprogramming of fibroblasts to cardiomyocytes.