Evidence map›Paper›PMID 31019236›Full record

ArticleScientific reports2019

Ensuring expression of four core cardiogenic transcription factors enhances cardiac reprogramming.

Zhentao Zhang, Alexander D Zhang, Luke J Kim, Young-Jae Nam

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 16% 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

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Pooled it
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  5. Article
  6. Review
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  12. Article
  13. The Future of Direct Cardiac Reprogramming: AnyInternational journal of molecular sciences · 2020
    Review
  14. Assessing Cardiac Reprogramming using High Content Imaging Analysis.Journal of visualized experiments : JoVE · 2020
    Article
  15. Review
  16. Article
  17. Review
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

4 authors at 2 institutions in 1 country.

Zhentao ZhangDepartment of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Alexander D ZhangDepartment of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Luke J KimDepartment of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Young-Jae NamDepartment of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. young-jae.nam@vanderbilt.edu.
Vanderbilt University · USVanderbilt University Medical Center · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
Cardiac repair by reprogramming fibroblasts into cardiomyocytesK08HL111420 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI NAM, YOUNG-JAE · 2012 to 2016
$660k
LSM880-Airyscan Confocal Microscope for Large Shared ResourceS10OD021630 · OD · VANDERBILT UNIVERSITY · PI WELLS, K. SAM · 2016 to 2016
$560k
Defining cardiomyocyte reprogramming induced heart repairR03HL140264 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI NAM, YOUNG-JAE · 2017 to 2018
$158k
NCI NIH HHS P30 CA068485NHLBI NIH HHS K08 HL111420NHLBI NIH HHS R03 HL140264NIH HHS S10 OD021630
6 · The paper itself

Abstract

Previous studies have shown that forced expression of core cardiogenic transcription factors can directly reprogram fibroblasts to induced cardiomyocyte-like cells (iCMs). This cardiac reprogramming approach suggests a potential strategy for cardiomyocyte regeneration. However, a major challenge of this approach remains the low conversion rate. Here, we showed that ensuring expression of four cardiogenic transcription factors (i.e. Gata4 (G), Hand2 (H), Mef2c (M), and Tbx5 (T)) in individual fibroblasts is an initial bottleneck for cardiac reprogramming. Following co-transduction of three or four retroviral vectors encoding individual cardiogenic transcription factors, only a minor subpopulation of cells indeed expressed all three (GMT) or four (GHMT) factors. By selectively analyzing subpopulations of cells expressing various combinations of reprogramming factors, we found that co-expression of GMT in individual fibroblasts is sufficient to induce sarcomeric proteins. However, only a small fraction of those cells expressing GMT were able to develop organized sarcomeric structures and contractility. In contrast, ensuring expression of GHMT markedly enhanced the development of contractile cardiac structures and functions in fibroblasts, although its incremental effect on sarcomeric protein induction was relatively small. Our findings provide new insights into the mechanistic basis of inefficient cardiac reprogramming and can help to devise efficient reprogramming strategies.

Indexed as

Cellular ReprogrammingAnimalsBasic Helix-Loop-Helix ProteinsCell DifferentiationCells, CulturedFibroblastsGATA4 Transcription FactorGene ExpressionMEF2 Transcription FactorsMice, Inbred C57BLMice, TransgenicMuscle ProteinsMyocytes, CardiacSarcomeresT-Box Domain ProteinsTranscription FactorsBasic Helix-Loop-Helix ProteinsGATA4 Transcription FactorHand2 protein, mouseMEF2 Transcription FactorsMuscle ProteinsT-Box Domain ProteinsT-box transcription factor 5Transcription Factors

Identifiers

PMID31019236
PMCPMC6482135
OpenAlexW2941621231

What OpenQuestion holds

Textmetadata
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.