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Cellular and Molecular Life Sciences

, Volume 74, Issue 12, pp 2203–2215 | Cite as

Discovery and progress of direct cardiac reprogramming

  • Hidenori Kojima
  • Masaki Ieda
Review

Abstract

Cardiac disease remains a major cause of death worldwide. Direct cardiac reprogramming has emerged as a promising approach for cardiac regenerative therapy. After the discovery of MyoD, a master regulator for skeletal muscle, other single cardiac reprogramming factors (master regulators) have been sought. Discovery of cardiac reprogramming factors was inspired by the finding that multiple, but not single, transcription factors were needed to generate induced pluripotent stem cells (iPSCs) from fibroblasts. We first reported a combination of cardiac-specific transcription factors, Gata4, Mef2c, and Tbx5 (GMT), that could convert mouse fibroblasts into cardiomyocyte-like cells, which were designated as induced cardiomyocyte-like cells (iCMs). Following our first report of cardiac reprogramming, many researchers, including ourselves, demonstrated an improvement in cardiac reprogramming efficiency, in vivo direct cardiac reprogramming for heart regeneration, and cardiac reprogramming in human cells. However, cardiac reprogramming in human cells and adult fibroblasts remains inefficient, and further efforts are needed. We believe that future research elucidating epigenetic barriers and molecular mechanisms of direct cardiac reprogramming will improve the reprogramming efficiency, and that this new technology has great potential for clinical applications.

Keywords

Fibroblast Regeneration Direct cardiac reprogramming Cardiomyocyte Transcription factor 

Abbreviations

GMT

Gata4, Mef2c, and Tbx5

GHMT

Gata4, Hand2, Mef2c, and Tbx5

iCMs

Induced cardiomyocyte-like cells

CFs

Cardiac fibroblasts

MEFs

Mouse embryonic fibroblasts

TTFs

Tail-tip fibroblasts

αMHC-GFP

αMyosin heavy chain promoter-driven enhanced green fluorescent protein

YFP

Yellow fluorescent protein

miRs

MicroRNAs

TGFβ

Transforming growth factorβ

VEGF

Vascular endothelial growth factors

FACS

Fluorescence-activated cell sorting; cTnT, cardiac troponin T

Notes

Acknowledgements

We are grateful to members of the Ieda laboratory for valuable discussion and contributions. M.I. was supported by research grants from AMED-PRIME, JSPS, Keio University Program for the Advancement of Next Generation Research Projects, Banyu Life Science, Senshin Medical Research Foundation, Takeda Science Foundation, and a Novartis Research Grant.

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Copyright information

© Springer International Publishing 2017

Authors and Affiliations

  1. 1.Department of CardiologyKeio University School of MedicineTokyoJapan
  2. 2.AMED-PRIMETokyoJapan

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