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Transcription factors MYOCD, SRF, Mesp1 and SMARCD3 enhance the cardio-inducing effect of GATA4, TBX5, and MEF2C during direct cellular reprogramming.

Publication ,  Journal Article
Christoforou, N; Chellappan, M; Adler, AF; Kirkton, RD; Wu, T; Addis, RC; Bursac, N; Leong, KW
Published in: PloS one
January 2013

Transient overexpression of defined combinations of master regulator genes can effectively induce cellular reprogramming: the acquisition of an alternative predicted phenotype from a differentiated cell lineage. This can be of particular importance in cardiac regenerative medicine wherein the heart lacks the capacity to heal itself, but simultaneously contains a large pool of fibroblasts. In this study we determined the cardio-inducing capacity of ten transcription factors to actuate cellular reprogramming of mouse embryonic fibroblasts into cardiomyocyte-like cells. Overexpression of transcription factors MYOCD and SRF alone or in conjunction with Mesp1 and SMARCD3 enhanced the basal but necessary cardio-inducing effect of the previously reported GATA4, TBX5, and MEF2C. In particular, combinations of five or seven transcription factors enhanced the activation of cardiac reporter vectors, and induced an upregulation of cardiac-specific genes. Global gene expression analysis also demonstrated a significantly greater cardio-inducing effect when the transcription factors MYOCD and SRF were used. Detection of cross-striated cells was highly dependent on the cell culture conditions and was enhanced by the addition of valproic acid and JAK inhibitor. Although we detected Ca(2+) transient oscillations in the reprogrammed cells, we did not detect significant changes in resting membrane potential or spontaneously contracting cells. This study further elucidates the cardio-inducing effect of the transcriptional networks involved in cardiac cellular reprogramming, contributing to the ongoing rational design of a robust protocol required for cardiac regenerative therapies.

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Published In

PloS one

DOI

EISSN

1932-6203

ISSN

1932-6203

Publication Date

January 2013

Volume

8

Issue

5

Start / End Page

e63577

Related Subject Headings

  • Transcriptome
  • Transcription, Genetic
  • Transcription Factors
  • Trans-Activators
  • T-Box Domain Proteins
  • Sus scrofa
  • Serum Response Factor
  • Organ Specificity
  • Oligonucleotide Array Sequence Analysis
  • Nuclear Proteins
 

Citation

APA
Chicago
ICMJE
MLA
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Christoforou, N., Chellappan, M., Adler, A. F., Kirkton, R. D., Wu, T., Addis, R. C., … Leong, K. W. (2013). Transcription factors MYOCD, SRF, Mesp1 and SMARCD3 enhance the cardio-inducing effect of GATA4, TBX5, and MEF2C during direct cellular reprogramming. PloS One, 8(5), e63577. https://doi.org/10.1371/journal.pone.0063577
Christoforou, Nicolas, Malathi Chellappan, Andrew F. Adler, Robert D. Kirkton, Tianyi Wu, Russell C. Addis, Nenad Bursac, and Kam W. Leong. “Transcription factors MYOCD, SRF, Mesp1 and SMARCD3 enhance the cardio-inducing effect of GATA4, TBX5, and MEF2C during direct cellular reprogramming.PloS One 8, no. 5 (January 2013): e63577. https://doi.org/10.1371/journal.pone.0063577.
Christoforou N, Chellappan M, Adler AF, Kirkton RD, Wu T, Addis RC, et al. Transcription factors MYOCD, SRF, Mesp1 and SMARCD3 enhance the cardio-inducing effect of GATA4, TBX5, and MEF2C during direct cellular reprogramming. PloS one. 2013 Jan;8(5):e63577.
Christoforou, Nicolas, et al. “Transcription factors MYOCD, SRF, Mesp1 and SMARCD3 enhance the cardio-inducing effect of GATA4, TBX5, and MEF2C during direct cellular reprogramming.PloS One, vol. 8, no. 5, Jan. 2013, p. e63577. Epmc, doi:10.1371/journal.pone.0063577.
Christoforou N, Chellappan M, Adler AF, Kirkton RD, Wu T, Addis RC, Bursac N, Leong KW. Transcription factors MYOCD, SRF, Mesp1 and SMARCD3 enhance the cardio-inducing effect of GATA4, TBX5, and MEF2C during direct cellular reprogramming. PloS one. 2013 Jan;8(5):e63577.

Published In

PloS one

DOI

EISSN

1932-6203

ISSN

1932-6203

Publication Date

January 2013

Volume

8

Issue

5

Start / End Page

e63577

Related Subject Headings

  • Transcriptome
  • Transcription, Genetic
  • Transcription Factors
  • Trans-Activators
  • T-Box Domain Proteins
  • Sus scrofa
  • Serum Response Factor
  • Organ Specificity
  • Oligonucleotide Array Sequence Analysis
  • Nuclear Proteins