Evidence map›Paper›PMID 25358788›Full record

ArticleStem cell reports2014

Acquisition of a quantitative, stoichiometrically conserved ratiometric marker of maturation status in stem cell-derived cardiac myocytes.

Fikru B Bedada, Sunny S-K Chan, Stefania K Metzger, Liying Zhang, Jianyi Zhang, Daniel J Garry, Timothy J Kamp, Michael Kyba, Joseph M Metzger

Abstract read
In one paragraph

Article in Stem cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers.

0numbers the graph read from it
0cells of the map it votes in
152citing papers in PubMed
–field-weighted citation impact
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

152 citing papers in PubMed.

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92 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

9 authors.

Fikru B BedadaDepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Sunny S-K ChanLillehei Heart Institute, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Stefania K MetzgerDepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Liying ZhangLillehei Heart Institute, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Jianyi ZhangLillehei Heart Institute, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Daniel J GarryLillehei Heart Institute, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Timothy J KampDepartment of Medicine, Stem Cell and Regenerative Medicine Center, University of Wisconsin, Madison, WI 53705, USA.
Michael KybaLillehei Heart Institute, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Joseph M MetzgerDepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA; Lillehei Heart Institute, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Electronic address: metzgerj@umn.edu.

Funding

Biorepository of Human iPSCs for Studying Dilated and Hypertrophic CardiomyopathyR24HL117756 · NHLBI · STANFORD UNIVERSITY · PI BUSTAMANTE, CARLOS DANIEL, SNYDER, MICHAEL P. · 2014 to 2018
$8.8M
Midwest Progenitor Cell ConsortiumU01HL099773 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI THOMSON, JAMES ALEXANDER · 2009 to 2015
$7.8M
Midwestern Progenitor Cell ConsortiumU01HL100407 · NHLBI · UNIVERSITY OF MINNESOTA · PI GARRY, DANIEL J., KYBA, MICHAEL · 2009 to 2015
$7.8M
Troponin and Heart Function in Heath and DiseaseR01HL059301 · NHLBI · UNIVERSITY OF MINNESOTA · PI METZGER, JOSEPH MARK · 1998 to 2014
$5.1M
Dystrophin Function in Aging HeartR01AG034107 · NIA · UNIVERSITY OF MINNESOTA · PI METZGER, JOSEPH MARK · 2010 to 2014
$1.7M
Regulatory Mechanisms of Endothelial Development and RegenerationR01HL122576 · NHLBI · UNIVERSITY OF MINNESOTA · PI GARRY, DANIEL J. · 2014 to 2017
$1.5M
PATHOPHYSIOLOGY OF CONSTITUTIVE A 1B-ADRENOCEPTOR ACTIONF32HL010004 · NHLBI · CLEVELAND CLINIC FOUNDATION · PI ZUSCIK, MICHAEL J · 1998 to 2000
$44k
NHLBI NIH HHS HL099773NHLBI NIH HHS NIH PCBC U01 HL1000407NHLBI NIH HHS R01 HL059301NHLBI NIH HHS R01 HL122576NHLBI NIH HHS R24 HL117756NHLBI NIH HHS U01 HL099773NHLBI NIH HHS U01 HL100407NIA NIH HHS R01 AG034107
6 · The paper itself

Abstract

There is no consensus in the stem cell field as to what constitutes the mature cardiac myocyte. Thus, helping formalize a molecular signature for cardiac myocyte maturation would advance the field. In the mammalian heart, inactivation of the "fetal" TNNI gene, TNNI1 (ssTnI), together in temporal concert with its stoichiometric replacement by the adult TNNI gene product, TNNI3 (cTnI), represents a quantifiable ratiometric maturation signature. We examined the TNNI isoform transition in human induced pluripotent stem cell (iPSC) cardiac myocytes (hiPSC-CMs) and found the fetal TNNI signature, even during long-term culture. Rodent stem cell-derived and primary myocytes, however, transitioned to the adult TnI profile. Acute genetic engineering of hiPSC-CMs enabled a rapid conversion toward the mature TnI profile. While there is no single marker to denote the mature cardiac myocyte, we propose that tracking the cTnI:ssTnI protein isoform ratio provides a valuable maturation signature to quantify myocyte maturation status across laboratories.

Indexed as

Cell DifferentiationAnimalsCells, CulturedEmbryonic Stem CellsHumansInduced Pluripotent Stem CellsMiceMyocytes, CardiacProtein IsoformsRatsRats, Sprague-DawleyTroponin IProtein IsoformsTroponin I

Identifiers

PMID25358788
PMCPMC4223713

What OpenQuestion holds

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Registered trials

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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.