Small molecules enable cardiac reprogramming of mouse fibroblasts with a single factor, oct4

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Abstract

It was recently shown that mouse fibroblasts could bereprogrammed into cells of a cardiac fate by forcedexpression of multiple transcription factors and microRNAs. For ultimate application of such a reprogramming strategy for cell-based therapy or invivo 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 the highly efficient conversion of mouse fibroblasts into cardiac cells with only one transcription factor, Oct4, without any evidence of entrance into the pluripotent state. Small-molecule-induced cardiomyocytes spontaneously contract and exhibit a ventricular phenotype. Furthermore, these induced cardiomyocytes pass through a cardiac progenitor stage. This study lays the foundation for future pharmacological reprogramming approaches and provides a small-molecule condition for investigation of the mechanisms underlying the cardiac reprogramming process. © 2014 The Authors.

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Wang, H., Cao, N., Spencer, C. I., Nie, B., Ma, T., Xu, T., … Ding, S. (2014). Small molecules enable cardiac reprogramming of mouse fibroblasts with a single factor, oct4. Cell Reports, 6(5), 951–960. https://doi.org/10.1016/j.celrep.2014.01.038

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