Evidence map›Paper›PMID 23704920›Full record

ArticlePloS one2013

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

Nicolas Christoforou, Malathi Chellappan, Andrew F Adler, Robert D Kirkton, Tianyi Wu, Russell C Addis, Nenad Bursac, Kam W Leong

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 1 pooled it
8.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

98 citing papers in PubMed, 1 synthesis or guideline pooled it, 165 citations in OpenAlex.

  1. Pooled it
  2. Spatial expression of myocardin protein in normal and disease states.American journal of physiology. Cell physiology · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Advances in fibroblast-based cardiac reprogramming in the treatment of heart disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Direct Cardiac Reprogramming in the Age of Computational Biology.Journal of cardiovascular development and disease · 2024
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Review

38 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Nicolas ChristoforouDepartment of Biomedical Engineering, Duke University, Durham, North Carolina, United States of America.
Malathi Chellappan
Andrew F Adler
Robert D Kirkton
Tianyi Wu
Russell C Addis
Nenad Bursac
Kam W Leong
Duke University · USCalifornia Institute for Regenerative Medicine · USThe University of Texas Southwestern Medical Center · US

Funding

Function and Integration of Stem Cell-derived Cardiac Tissue PatchR01HL104326 · NHLBI · DUKE UNIVERSITY · PI BURSAC, NENAD · 2010 to 2014
$1.8M
Tissue-engineered Autonomous PacemakerR21HL106203 · NHLBI · DUKE UNIVERSITY · PI BURSAC, NENAD · 2011 to 2012
$421k
NHLBI NIH HHS R01 HL104326NHLBI NIH HHS R01HL104326NHLBI NIH HHS R21 HL106203NHLBI NIH HHS R21HL106203
6 · The paper itself

Abstract

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.

Indexed as

Cellular ReprogrammingAnimalsBasic Helix-Loop-Helix ProteinsChromosomal Proteins, Non-HistoneCytoskeletonElectrophysiological PhenomenaEmbryo, MammalianFibroblastsGATA4 Transcription FactorGene Expression RegulationGene Regulatory NetworksMEF2 Transcription FactorsMiceMice, Inbred C57BLMice, TransgenicMuscle ProteinsBasic Helix-Loop-Helix ProteinsChromosomal Proteins, Non-HistoneGATA4 Transcription FactorMEF2 Transcription FactorsMesp1 protein, mouseMuscle ProteinsMyocardinNuclear ProteinsSerum Response FactorSmarcd3 protein, mouseT-Box Domain ProteinsT-box transcription factor 5Trans-ActivatorsTranscription Factors

Identifiers

PMID23704920
PMCPMC3660533
OpenAlexW2075134815

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.