Evidence map›Paper›PMID 30464173›Full record

ArticleNature communications2018

Defining human cardiac transcription factor hierarchies using integrated single-cell heterogeneity analysis.

Jared M Churko, Priyanka Garg, Barbara Treutlein, Meenakshi Venkatasubramanian, Haodi Wu, Jaecheol Lee, Quinton N Wessells, Shih-Yu Chen, Wen-Yi Chen, Kashish Chetal and 7 more

Abstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
135citing papers in PubMed, 1 pooled it
–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

135 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Germline variants in HEY2 functional domains lead to congenital heart defects and thoracic aortic aneurysms.Genetics in medicine : official journal of the American College of Medical Genetics · 2021
    Pooled it
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75 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

17 authors.

Jared M ChurkoStanford Cardiovascular Institute, Stanford University, Stanford, CA, 94305, USA. jchurko@email.arizona.edu.
Priyanka GargStanford Cardiovascular Institute, Stanford University, Stanford, CA, 94305, USA.
Barbara TreutleinDepartment of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
Meenakshi VenkatasubramanianDivision of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
Haodi WuStanford Cardiovascular Institute, Stanford University, Stanford, CA, 94305, USA.
Jaecheol LeeStanford Cardiovascular Institute, Stanford University, Stanford, CA, 94305, USA.
Quinton N WessellsStanford Cardiovascular Institute, Stanford University, Stanford, CA, 94305, USA.
Shih-Yu ChenBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Wen-Yi ChenStanford Cardiovascular Institute, Stanford University, Stanford, CA, 94305, USA.
Kashish ChetalDivision of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
Gary MantalasDepartment of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
Norma NeffDepartment of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
Eric JabartZephyrus Biosciences, Inc. 820 Heinz Ave, Berkeley, CA, 94710, USA.
Arun SharmaStanford Cardiovascular Institute, Stanford University, Stanford, CA, 94305, USA.ORCID http://orcid.org/0000-0002-0607-5455
Garry P NolanBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Nathan SalomonisDivision of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA. nathan.salomonis@cchmc.org.
Joseph C WuStanford Cardiovascular Institute, Stanford University, Stanford, CA, 94305, USA. joewu@stanford.edu.

Funding

Elucidating Mechanism of Cardiac Fibrosis with Cell Village of Pooled Human iPSCsR01HL130020 · NHLBI · STANFORD UNIVERSITY · PI Ronglih Liao, MARK MERCOLA · 2016 to 2026
$7.3M
Human iPSCs for Elucidating Intercellular Crosstalk Signaling in Dilated CardiomyopathyR01HL141371 · NHLBI · STANFORD UNIVERSITY · PI WONG, WING H., WU, JOSEPH C. · 2018 to 2025
$6.2M
Modeling Tyrosine Kinase Inhibitor-Induced Vascular Dysfunction Using Human iPSCsR01HL141851 · NHLBI · STANFORD UNIVERSITY · PI WONG, WING H., WU, JOSEPH C. · 2018 to 2025
$5.7M
Modeling Susceptibility to Chemotherapy-Induced Cardiotoxicity Using Human iPSCsR01HL123968 · NHLBI · STANFORD UNIVERSITY · PI QUERTERMOUS, THOMAS, WU, JOSEPH C. · 2014 to 2021
$4.8M
A Systems Biology Approach to Study Cardiac Arrhythmias: iPS Cells and In Silico ModelingR01HL128170 · NHLBI · STANFORD UNIVERSITY · PI ALTMAN, RUSS BIAGIO, CLANCY, COLLEEN E · 2015 to 2018
$3.0M
Notch signaling in cardiomyocyte transcriptome signaturesR00HL128906 · NHLBI · UNIVERSITY OF ARIZONA · PI CHURKO, JARED · 2018 to 2020
$704k
Notch signaling in cardiomyocyte transcriptome signaturesK99HL128906 · NHLBI · STANFORD UNIVERSITY · PI CHURKO, JARED · 2015 to 2016
$230k
NHLBI NIH HHS K99 HL128906NHLBI NIH HHS R00 HL128906NHLBI NIH HHS R01 HL123968NHLBI NIH HHS R01 HL128170NHLBI NIH HHS R01 HL130020NHLBI NIH HHS R01 HL141371NHLBI NIH HHS R01 HL141851
6 · The paper itself

Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have become a powerful tool for human disease modeling and therapeutic testing. However, their use remains limited by their immaturity and heterogeneity. To characterize the source of this heterogeneity, we applied complementary single-cell RNA-seq and bulk RNA-seq technologies over time during hiPSC cardiac differentiation and in the adult heart. Using integrated transcriptomic and splicing analysis, more than half a dozen distinct single-cell populations were observed, several of which were coincident at a single time-point, day 30 of differentiation. To dissect the role of distinct cardiac transcriptional regulators associated with each cell population, we systematically tested the effect of a gain or loss of three transcription factors (NR2F2, TBX5, and HEY2), using CRISPR genome editing and ChIP-seq, in conjunction with patch clamp, calcium imaging, and CyTOF analysis. These targets, data, and integrative genomics analysis methods provide a powerful platform for understanding in vitro cellular heterogeneity.

Indexed as

Cell DifferentiationGenetic HeterogeneityAction PotentialsBasic Helix-Loop-Helix ProteinsCalcium SignalingCOUP Transcription Factor IIHumansInduced Pluripotent Stem CellsMyocytes, CardiacRepressor ProteinsSequence Analysis, RNASingle-Cell AnalysisT-Box Domain ProteinsTranscriptomeBasic Helix-Loop-Helix ProteinsCOUP Transcription Factor IIHEY2 protein, humanNR2F2 protein, humanRepressor ProteinsT-Box Domain ProteinsT-box transcription factor 5

Identifiers

PMID30464173
PMCPMC6249224

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.