Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes by Defined Factors

By M. Ieda, Ji-Dong Fu, P. Delgado-Olguín, V. Vedantham, Y. Hayashi, B. Bruneau, Deepak Srivastava. Cell, 2010

2,435 citations recorded by the source corpus.

SUMMARY The reprogramming of fibroblasts to induced pluripotent stem (iPS) cells raises the possibility that a somatic cell could be reprogrammed to an alternative differentiated fate without first becoming a stem/progenitor cell. A large pool of fibroblasts exists in the post-natal heart, yet no single “master regulator” of direct cardiac reprogramming has been identified. Here, we report that a combination of three developmental transcription factors (i.e., Gata4, Mef2c and Tbx5) rapidly and efficiently reprogrammed post-natal cardiac or dermal fibroblasts directly into differentiated cardiomyocyte-like cells. Induced cardiomyocytes expressed cardiac-specific markers, had a global gene expression profile similar to cardiomyocytes, and contracted spontaneously. Fibroblasts transplanted into mouse hearts one day after transduction of the three factors also differentiated into cardiomyocyte-like cells. These findings demonstrate that functional cardiomyocytes can be directly reprogrammed from differentiated somatic cells by defined factors. Reprogramming of endogenous or explanted fibroblasts might provide a source of cardiomyocytes for regenerative approaches.

Subfields: Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/696ab3d5fb53db1cf35407788786fae5041482a5

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Citations in the corpus

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Somatic cell reprogramming and transitions between pluripotent states: facts, hypotheses, unresolved issues (2010, positive): “Recently, cardiac fibroblasts were elegantly converted into cardiomyocyte-like cells by the ectopic expression of Gata4, Mef2C, and Tbx5 (Ieda et al., 2010).”