Article | Published:

Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy

Nature Cell Biology volume 13, pages 215222 (2011) | Download Citation

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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Change history

  • Corrected online 11 February 2011

    In the version of this article initially published online, the commerically available cardiomyocytes Cor.At were incorrectly referred to as CorAT in Figure 4. Similarly, in the methods Axiogenesis was not correctly referenced as the manufacturers of Cor.At cells. This error has been corrected in both the HTML and PDF versions of the article.

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Acknowledgements

We thank C. Desponts, X. Yuan, S. Zhu, R. Ambasudhan, R. Abujarour and W. Li for discussions, technical assistance, and critical reading of the manuscript. We also thank H. Schöler for providing TTFs, and D. Watry for assistance with FACS analyses. S.D. is supported by funding from NICHD, NHLBI and NIMH/NIH, California Institute for Regenerative Medicine, Prostate Cancer Foundation, Fate Therapeutics, Esther B. O'Keeffe Foundation and the Scripps Research Institute. J.A.E. is a Lowe Family Foundation fellow.

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Affiliations

  1. Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

    • Jem A. Efe
    • , Simon Hilcove
    • , Janghwan Kim
    • , Hongyan Zhou
    •  & Sheng Ding
  2. Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA.

    • Kunfu Ouyang
    • , Gang Wang
    •  & Ju Chen

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Contributions

J.A.E. and S.D. conceived the project and wrote the manuscript. J.A.E. designed and carried out experiments. S.H., J.K., H.Z., K.O., G.W. and J.C. provided materials and assisted with experiments.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Sheng Ding.

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DOI

https://doi.org/10.1038/ncb2164