Evidence map›Paper›PMID 25416133›Full record

ArticleCirculation research2015

Stoichiometry of Gata4, Mef2c, and Tbx5 influences the efficiency and quality of induced cardiac myocyte reprogramming.

Li Wang, Ziqing Liu, Chaoying Yin, Huda Asfour, Olivia Chen, Yanzhen Li, Nenad Bursac, Jiandong Liu, Li Qian

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
157citing papers in PubMed, 1 pooled it
9.4field-weighted citation impact, top 1% 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

157 citing papers in PubMed, 1 synthesis or guideline pooled it, 231 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Frontiers in cell and developmental biology · 2026
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. 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
  12. Review
  13. Review
  14. Article
  15. Article
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  17. Article
  18. Enhanced fatty acid oxidation via SCD1 downregulation fuels cardiac reprogramming.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  19. Review
  20. Cell reprogramming: methods, mechanisms and applications.Cell regeneration (London, England) · 2025
    Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Li WangFrom the Department of Pathology and Laboratory Medicine (L.W., Z.L., C.Y., O.C., J.L., L.Q.), McAllister Heart Institute (L.W., Z.L., C.Y., O.C., J.L., L.Q,), and Lineberger Comprehensive Cancer Center (L.W., Z.L., C.Y., O.C., J.L., L.Q.), University of North Carolina, Chapel Hill; and Department of Biomedical Engineering, Duke University, Durham, NC (H.A., Y.L., N.B.).
Ziqing LiuFrom the Department of Pathology and Laboratory Medicine (L.W., Z.L., C.Y., O.C., J.L., L.Q.), McAllister Heart Institute (L.W., Z.L., C.Y., O.C., J.L., L.Q,), and Lineberger Comprehensive Cancer Center (L.W., Z.L., C.Y., O.C., J.L., L.Q.), University of North Carolina, Chapel Hill; and Department of Biomedical Engineering, Duke University, Durham, NC (H.A., Y.L., N.B.).
Chaoying YinFrom the Department of Pathology and Laboratory Medicine (L.W., Z.L., C.Y., O.C., J.L., L.Q.), McAllister Heart Institute (L.W., Z.L., C.Y., O.C., J.L., L.Q,), and Lineberger Comprehensive Cancer Center (L.W., Z.L., C.Y., O.C., J.L., L.Q.), University of North Carolina, Chapel Hill; and Department of Biomedical Engineering, Duke University, Durham, NC (H.A., Y.L., N.B.).
Huda AsfourFrom the Department of Pathology and Laboratory Medicine (L.W., Z.L., C.Y., O.C., J.L., L.Q.), McAllister Heart Institute (L.W., Z.L., C.Y., O.C., J.L., L.Q,), and Lineberger Comprehensive Cancer Center (L.W., Z.L., C.Y., O.C., J.L., L.Q.), University of North Carolina, Chapel Hill; and Department of Biomedical Engineering, Duke University, Durham, NC (H.A., Y.L., N.B.).
Olivia ChenFrom the Department of Pathology and Laboratory Medicine (L.W., Z.L., C.Y., O.C., J.L., L.Q.), McAllister Heart Institute (L.W., Z.L., C.Y., O.C., J.L., L.Q,), and Lineberger Comprehensive Cancer Center (L.W., Z.L., C.Y., O.C., J.L., L.Q.), University of North Carolina, Chapel Hill; and Department of Biomedical Engineering, Duke University, Durham, NC (H.A., Y.L., N.B.).
Yanzhen LiFrom the Department of Pathology and Laboratory Medicine (L.W., Z.L., C.Y., O.C., J.L., L.Q.), McAllister Heart Institute (L.W., Z.L., C.Y., O.C., J.L., L.Q,), and Lineberger Comprehensive Cancer Center (L.W., Z.L., C.Y., O.C., J.L., L.Q.), University of North Carolina, Chapel Hill; and Department of Biomedical Engineering, Duke University, Durham, NC (H.A., Y.L., N.B.).
Nenad BursacFrom the Department of Pathology and Laboratory Medicine (L.W., Z.L., C.Y., O.C., J.L., L.Q.), McAllister Heart Institute (L.W., Z.L., C.Y., O.C., J.L., L.Q,), and Lineberger Comprehensive Cancer Center (L.W., Z.L., C.Y., O.C., J.L., L.Q.), University of North Carolina, Chapel Hill; and Department of Biomedical Engineering, Duke University, Durham, NC (H.A., Y.L., N.B.).
Jiandong LiuFrom the Department of Pathology and Laboratory Medicine (L.W., Z.L., C.Y., O.C., J.L., L.Q.), McAllister Heart Institute (L.W., Z.L., C.Y., O.C., J.L., L.Q,), and Lineberger Comprehensive Cancer Center (L.W., Z.L., C.Y., O.C., J.L., L.Q.), University of North Carolina, Chapel Hill; and Department of Biomedical Engineering, Duke University, Durham, NC (H.A., Y.L., N.B.).
Li QianFrom the Department of Pathology and Laboratory Medicine (L.W., Z.L., C.Y., O.C., J.L., L.Q.), McAllister Heart Institute (L.W., Z.L., C.Y., O.C., J.L., L.Q,), and Lineberger Comprehensive Cancer Center (L.W., Z.L., C.Y., O.C., J.L., L.Q.), University of North Carolina, Chapel Hill; and Department of Biomedical Engineering, Duke University, Durham, NC (H.A., Y.L., N.B.). li_qian@med.unc.edu.
Council of Independent Colleges · US

Funding

SHORT-TERM RESEARCH TRAININGT35DK007386 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Evan Samuel Dellon · 1986 to 2026
$4.1M
Function and Integration of Stem Cell-derived Cardiac Tissue PatchR01HL104326 · NHLBI · DUKE UNIVERSITY · PI BURSAC, NENAD · 2010 to 2014
$1.8M
Role of hemodynamics and ErbB signaling in cardiac trabeculationR00HL109079 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LIU, JIANDONG · 2013 to 2015
$742k
NHLBI NIH HHS 1R01HL104326NHLBI NIH HHS R00 HL109079NHLBI NIH HHS R01 HL104326NIDDK NIH HHS T35-DK007386
6 · The paper itself

Abstract

rationaleGeneration of induced cardiac myocytes (iCMs) directly from fibroblasts offers great opportunities for cardiac disease modeling and cardiac regeneration. A major challenge of iCM generation is the low conversion rate of fibroblasts to fully reprogrammed iCMs, which could in part be attributed to unbalanced expression of reprogramming factors Gata4 (G), Mef2c (M), and Tbx5 (T) using the current gene delivery approach.

objectiveWe aimed to establish a system to express distinct ratios of G, M, T proteins in fibroblasts and determine the effect of G, M, T stoichiometry on iCM reprogramming. METHODS AND

resultsWe took advantage of the inherent feature of the polycistronic system and generated all possible combinations of G, M, T with identical 2A sequences in a single transgene. We demonstrated that each splicing order of G, M, T gave rise to distinct G, M, T protein expression levels. Combinations that resulted in higher protein level of Mef2c with lower levels of Gata4 and Tbx5 significantly enhanced reprogramming efficiency compared with separate G, M, T transduction. Importantly, after further optimization, the MGT vector resulted in more than 10-fold increase in the number of mature beating iCM loci. Molecular characterization revealed that more optimal G, M, T stoichiometry correlated with higher expression of mature cardiac myocyte markers.

conclusionsOur results demonstrate that stoichiometry of G, M, T protein expression influences the efficiency and quality of iCM reprogramming. The established optimal G, M, T expression condition will provide a valuable platform for future iCM studies.

Indexed as

AnimalsCells, CulturedCellular ReprogrammingGATA4 Transcription FactorMEF2 Transcription FactorsMiceMice, TransgenicMyocytes, CardiacT-Box Domain ProteinsGata4 protein, mouseGATA4 Transcription FactorMef2c protein, mouseMEF2 Transcription FactorsT-Box Domain ProteinsT-box transcription factor 5fibroblastsGata4 proteingene expression/regulationMef2c proteinmyocytes, cardiacregenerationTbx5 proteintranscription factors

Identifiers

PMID25416133
PMCPMC4299697
OpenAlexW2108862261

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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.