Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy

JA Efe, S Hilcove, J Kim, H Zhou, K Ouyang… - Nature cell …, 2011 - nature.com
JA Efe, S Hilcove, J Kim, H Zhou, K Ouyang, G Wang, J Chen, S Ding
Nature cell biology, 2011nature.com
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 …
Abstract
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.
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