期刊
CELL RESEARCH
卷 25, 期 9, 页码 1013-1024出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cr.2015.99
关键词
transdifferentiation; cardiac reprogramming; cardiomyocyte; fibroblast; chemical cocktail; small molecule compounds
类别
资金
- Chinese Academy of Sciences [XDA01040301]
- Ministry of Science and Technology of China [2015CB964503]
- National Natural Science Foundation of China [81425024, 31371511]
The direct conversion, or transdifferentiation, of non-cardiac cells into cardiomyocytes by forced expression of transcription factors and microRNAs provides promising approaches for cardiac regeneration. However, genetic manipulations raise safety concerns and are thus not desirable in most clinical applications. The discovery of full chemically induced pluripotent stem cells suggest the possibility of replacing transcription factors with chemical cocktails. Here, we report the generation of automatically beating cardiomyocyte-like cells from mouse fibroblasts using only chemical cocktails. These chemical-induced cardiomyocyte-like cells (CiCMs) express cardiomyocyte-specific markers, exhibit sarcomeric organization, and possess typical cardiac calcium flux and electrophysiological features. Genetic lineage tracing confirms the fibroblast origin of these CiCMs. Further studies show the generation of CiCMs passes through a cardiac progenitor stage instead of a pluripotent stage. Bypassing the use of viral-derived factors, this proof of concept study lays a foundation for in vivo cardiac transdifferentiation with pharmacological agents and possibly safer treatment of heart failure.
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