Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, San Francisco, CA 94158, USA.
Cell. 2010 Aug 6;142(3):375-86. doi: 10.1016/j.cell.2010.07.002.
The reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs) raises the possibility that a somatic cell could be reprogrammed to an alternative differentiated fate without first becoming a stem/progenitor cell. A large pool of fibroblasts exists in the postnatal heart, yet no single "master regulator" of direct cardiac reprogramming has been identified. Here, we report that a combination of three developmental transcription factors (i.e., Gata4, Mef2c, and Tbx5) rapidly and efficiently reprogrammed postnatal cardiac or dermal fibroblasts directly into differentiated cardiomyocyte-like cells. Induced cardiomyocytes expressed cardiac-specific markers, had a global gene expression profile similar to cardiomyocytes, and contracted spontaneously. Fibroblasts transplanted into mouse hearts one day after transduction of the three factors also differentiated into cardiomyocyte-like cells. We believe these findings demonstrate that functional cardiomyocytes can be directly reprogrammed from differentiated somatic cells by defined factors. Reprogramming of endogenous or explanted fibroblasts might provide a source of cardiomyocytes for regenerative approaches.
成纤维细胞重编程为诱导多能干细胞（iPSCs）提出了一种可能性，即体细胞可以在不首先成为干细胞/祖细胞的情况下被重编程为另一种分化命运。在出生后的心脏中存在大量的成纤维细胞，但尚未鉴定出单一的“主调控因子”来直接进行心脏重编程。在这里，我们报告说，三种发育转录因子（即 Gata4、Mef2c 和 Tbx5）的组合可以快速有效地将出生后心脏或皮肤成纤维细胞直接重编程为分化的心肌细胞样细胞。诱导的心肌细胞表达心脏特异性标志物，具有与心肌细胞相似的全基因表达谱，并自发收缩。在转导三种因子一天后移植到小鼠心脏中的成纤维细胞也分化为心肌细胞样细胞。我们相信这些发现表明，可以通过定义的因子直接从分化的体细胞中重新编程功能性心肌细胞。内源性或移植的成纤维细胞的重编程可能为再生方法提供心肌细胞的来源。
