Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy

Abstract

Reprogramming cells towards pluripotency by expression of Oct4, Sox2, Klf4 and c-Myc can be directed towards cardiogenesis by changing the cell culture medium, leading to the formation of spontaneously contracting patches of differentiated cardiomyocytes within ten days. 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.

Cite this article

Efe, J., Hilcove, S., Kim, J. et al. Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy. Nat Cell Biol 13, 215–222 (2011). https://doi.org/10.1038/ncb2164

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