Evidence map›Paper›PMID 31628386›Full record

ArticleScientific reports2019

Stoichiometric optimization of Gata4, Hand2, Mef2c, and Tbx5 expression for contractile cardiomyocyte reprogramming.

Zhentao Zhang, Wenhui Zhang, 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 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 19% 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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Pooled it
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  15. The Future of Direct Cardiac Reprogramming: AnyInternational journal of molecular sciences · 2020
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  16. Assessing Cardiac Reprogramming using High Content Imaging Analysis.Journal of visualized experiments : JoVE · 2020
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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

3 authors at 2 institutions in 1 country.

Zhentao ZhangDepartment of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Wenhui ZhangDepartment 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 Medical Center · USVanderbilt University · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STACIE B DUSETZINA · 1995 to 2026
$172.8M
Targeting myofibroblasts for heart repairR01HL146524 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI NAM, YOUNG-JAE · 2019 to 2022
$1.7M
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 R01 HL146524NHLBI NIH HHS R03 HL140264NIH HHS S10 OD021630
6 · The paper itself

Abstract

Reprogramming of fibroblasts to induced cardiomyocyte-like cells (iCMs) offers potential strategies for new cardiomyocyte generation. However, a major challenge of this approach remains its low efficiency for contractile iCMs. Here, we showed that controlled stoichiometric expression of Gata4 (G), Hand2 (H), Mef2c (M), and Tbx5 (T) significantly enhanced contractile cardiomyocyte reprogramming over previously defined stoichiometric expression of GMT or uncontrolled expression of GHMT. We generated quad-cistronic vectors expressing distinct relative protein levels of GHMT within the context of a previously defined splicing order of M-G-T with high Mef2c level. Transduction of the quad-cistronic vector with a splicing order of M-G-T-H (referred to as M-G-T-H) inducing relatively low Hand2 and high Mef2c protein levels not only increased sarcomeric protein induction, but also markedly promoted the development of contractile structures and functions in fibroblasts. The expressed Gata4 and Tbx5 protein levels by M-G-T-H transduction were relatively higher than those by transductions of other quad-cistronic vectors, but lower than those by previously defined M-G-T tri-cistronic vector transduction. Taken together, our results demonstrate the stoichiometric requirement of GHMT expression for structural and functional progresses of cardiomyocyte reprogramming and provide a new basic tool-set for future studies.

Indexed as

AnimalsBasic Helix-Loop-Helix ProteinsCells, CulturedCellular ReprogrammingFibroblastsGATA4 Transcription FactorMEF2 Transcription FactorsMiceMice, TransgenicMyocardial ContractionMyocytes, CardiacPhenotypePlasmidsT-Box Domain ProteinsTranscriptomeTransduction, GeneticBasic Helix-Loop-Helix ProteinsGata4 protein, mouseGATA4 Transcription FactorHand2 protein, mouseMef2c protein, mouseMEF2 Transcription FactorsT-Box Domain ProteinsT-box transcription factor 5

Identifiers

PMID31628386
PMCPMC6800441
OpenAlexW2981302060

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.