Direct reprogramming of human fibroblasts into cardiomyocyte-like cells

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Direct reprogramming of differentiated human somatic cells into cardiac cells holds great promise for regenerative medicine. It has not been whether human fibroblasts can be directly reprogrammed into differentiated cardiomyocytes by defined factors. Here, we demonstrate that Gata4, Mef2c, and Tbx5 could also convert postnatal human cardiac fibroblasts directly into cardiomyocyte-like cells, when combined with two additional cardiac transcriptional regulators. Human induced cardiac cells expressed multiple cardiac-specific markers, changed a global gene expression profile toward a cardiomyocyte-like state, and generated spontaneous Ca transients. Importantly, a subset of induced cardiac cells matured to exhibit action potentials and contracted synchronously when co-cultured with primary murine cardiomyocytes. Thus, human fibroblasts can be converted into cardiomyocyte-like cells and these methods may facilitate future applications in regenerative purposes.