Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Nat Cell Biol. 2011 Mar;13(3):215-22. doi: 10.1038/ncb2164. Epub 2011 Jan 30.
Here we show that conventional reprogramming towards pluripotency through overexpression of Oct4, Sox2, Klf4 and c-Myc can be shortcut and directed towards cardiogenesis in a fast and efficient manner. With as little as 4 days of transgenic expression of these factors, mouse embryonic fibroblasts (MEFs) can be directly reprogrammed to spontaneously contracting patches of differentiated cardiomyocytes over a period of 11-12 days. Several lines of evidence suggest that a pluripotent intermediate is not involved. Our method represents a unique strategy that allows a transient, plastic developmental state established early in reprogramming to effectively function as a cellular transdifferentiation platform, the use of which could extend beyond cardiogenesis. Our study has potentially wide-ranging implications for induced pluripotent stem cell (iPSC)-factor-based reprogramming and broadens the existing paradigm.
在这里，我们展示了通过过表达 Oct4、Sox2、Klf4 和 c-Myc 来进行传统的多能性重编程可以被快速有效地简化为心肌发生方向。通过仅仅 4 天的这些因子的转基因表达，小鼠胚胎成纤维细胞（MEFs）可以在 11-12 天的时间内直接被重编程为自发收缩的分化心肌细胞斑块。有几条证据表明，中间多能性并不参与其中。我们的方法代表了一种独特的策略，允许在重编程早期建立的短暂、可塑性发育状态有效地作为细胞转分化平台发挥作用，其用途可能不仅限于心肌发生。我们的研究对于基于诱导多能干细胞（iPSC）因子的重编程具有潜在的广泛影响，并拓宽了现有的范例。
