Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes by Defined Factors

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2010 Aug 10

PMID 20691899

Citations 1209

Authors

Masaki Ieda

Ji-Dong Fu

Paul Delgado-Olguin

Vasanth Vedantham

Yohei Hayashi

Benoit G Bruneau

Deepak Srivastava

Affiliations

Soon will be listed here.

Abstract

The reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs) 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 postnatal 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 postnatal 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. We believe 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.

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