Accelerated direct reprogramming of fibroblasts into cardiomyocyte-like cells with the MyoD transactivation domain

Hiroyuki Hirai, Nobuko Katoku-Kikyo, Susan A. Keirstead, Nobuaki Kikyo

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Aims: Fibroblasts can be directly reprogrammed tocardiomyocyte-like cells by introducing defined genes. However, the repro-gramming efficiency remains low, delaying the clinical application of this strategy to regenerative cardiology. We previously showed that fusion of the MyoD transactivation domain to the pluripotency transcription factor Oct4 facilitated the transcriptional activity of Oct 4, resulting in highly efficient production of induced pluripotent stem cells. Weexamined whether the same approach can be applied to cardiac transcription factors to facilitate cardiac reprogramming. Methods and results: We fused the MyoD domain to Mef2c, Gata4, Hand2, and Tbx5 and transduced these genes in various combinations into mouse non-cardiac fibroblasts. Transduction of the chimeric Mef2c with the wild-types of the other three genes produced much larger beating clusters of cardiomyocyte-like cells faster than the combination of the four wild-type genes, with an efficiency of 3.5%, >15-fold greater than the wild-type genes. Conclusion: Fusion of a powerful transactivation domain to heterologous factors can increase the efficiency of direct reprogramming of fibroblasts to cardiomyocytes.

Original languageEnglish (US)
Pages (from-to)105-113
Number of pages9
JournalCardiovascular Research
Volume100
Issue number1
DOIs
StatePublished - Oct 1 2013

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Cardiac Myocytes
Transcriptional Activation
Fibroblasts
Genes
Transcription Factors
Induced Pluripotent Stem Cells
Cardiology

Keywords

  • Cardiomyocytes
  • Direct reprogramming
  • Transcription factors

Cite this

Accelerated direct reprogramming of fibroblasts into cardiomyocyte-like cells with the MyoD transactivation domain. / Hirai, Hiroyuki; Katoku-Kikyo, Nobuko; Keirstead, Susan A.; Kikyo, Nobuaki.

In: Cardiovascular Research, Vol. 100, No. 1, 01.10.2013, p. 105-113.

Research output: Contribution to journalArticle

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