Small molecules enable cardiac reprogramming of mouse fibroblasts with a single factor, Oct4.
Small molecules enable cardiac reprogramming of mouse fibroblasts with a single factor, Oct4.
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DOI：
10.1016/j.celrep.2014.01.038
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发表时间：
2014-03-13
期刊：
影响因子：
8.8
通讯作者：
Ding S
中科院分区：
文献类型：
--
作者：
Wang H;Cao N;Spencer CI;Nie B;Ma T;Xu T;Zhang Y;Wang X;Srivastava D;Ding S
最近的研究表明，通过多种转录因子和microRNAs的强制表达，小鼠成纤维细胞可以被重新编程为具有心脏命运的细胞。为了最终将这种重编程策略应用于基于细胞的治疗或体内心脏再生，减少或消除小分子的遗传操作将是非常可取的。在这里，我们报告了一种定义的小分子鸡尾酒的鉴定，该鸡尾酒能够使小鼠成纤维细胞高效地转化为心脏细胞，只需一种转录因子Oct4，而不需要进入多能状态。小分子诱导的心肌细胞自发收缩并表现为室性表型。此外，在我们的条件下，这种诱导的心肌细胞会经历心脏祖细胞阶段。这项研究为未来的药物重编程方法奠定了基础，并为研究心脏重编程过程的机制提供了一个新的小分子条件。
It was recently shown that mouse fibroblasts could be reprogrammed into cells of a cardiac fate by forced expression of multiple transcription factors and microRNAs. To ultimately apply such reprogramming strategy for cell-based therapy or in vivo cardiac regeneration, reducing or eliminating the genetic manipulations by small molecules would be highly desirable. Here, we report the identification of a defined small-molecule cocktail that enables highly efficient conversion of mouse fibroblasts into cardiac cells with only one transcription factor, Oct4, without entering the pluripotent state. Small-molecule-induced cardiomyocytes spontaneously contract and exhibit a ventricular phenotype. Furthermore, such induced cardiomyocytes under our condition pass through a cardiac progenitor stage. This study lays the foundation for future pharmacological reprogramming approaches and provides a novel small-molecule condition to investigate the mechanisms underlying cardiac reprogramming process.