Evidence map›Paper›PMID 31402282›Full record

ArticleDevelopmental cell2019

Canonical Wnt5b Signaling Directs Outlying Nkx2.5+ Mesoderm into Pacemaker Cardiomyocytes.

Jie Ren, Peidong Han, Xuanyi Ma, Elie N Farah, Joshua Bloomekatz, Xin-Xin I Zeng, Ruilin Zhang, Megan M Swim, Alec D Witty, Hannah G Knight and 5 more

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

Article in Developmental cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

61 citing papers in PubMed, 94 citations in OpenAlex.

  1. Review
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  7. Promoting differentiation of human-induced pluripotent stem cells into sinoatrial node-like cells through programmed regulation of AMPK signalling pathway.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025
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  17. The molecular mechanisms of cardiac development and related diseases.Signal transduction and targeted therapy · 2024
    Review
  18. Article
  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 1 country.

Jie RenDepartment of Medicine, Division of Cardiology, University of California, San Diego, La Jolla, CA 92093, USA.
Peidong HanDepartment of Medicine, Division of Cardiology, University of California, San Diego, La Jolla, CA 92093, USA.
Xuanyi MaDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Elie N FarahDepartment of Medicine, Division of Cardiology, University of California, San Diego, La Jolla, CA 92093, USA.
Joshua BloomekatzDepartment of Medicine, Division of Cardiology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Biology, University of Mississippi, Oxford, MS 38677, USA.
Xin-Xin I ZengDivision of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Ruilin ZhangDepartment of Medicine, Division of Cardiology, University of California, San Diego, La Jolla, CA 92093, USA.
Megan M SwimDepartment of Medicine, Division of Cardiology, University of California, San Diego, La Jolla, CA 92093, USA.
Alec D WittyDepartment of Medicine, Division of Cardiology, University of California, San Diego, La Jolla, CA 92093, USA.
Hannah G KnightDivision of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Rima DeshpandeDepartment of Medicine, Division of Cardiology, University of California, San Diego, La Jolla, CA 92093, USA.
Weizhe XuDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Deborah YelonDivision of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Shaochen ChenDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA; Department of NanoEngineering, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Neil C ChiDepartment of Medicine, Division of Cardiology, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: nchi@ucsd.edu.
University of California, San Diego · USUniversity of Mississippi · US

Funding

Administrative Coordinating Center: Cardiovascular Development and Pediatric Cardiac Genomics ConsortiaU01HL131003 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI CNOTA, JAMES, OLLBERDING, NICHOLAS J · 2016 to 2024
$54.8M
Developmental Regulatory Genomics of Human Cardiovascular LineagesUM1HL128773 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C, EVANS, SYLVIA M · 2015 to 2019
$3.8M
Genetic Regulation of Outflow Tract Formation in ZebrafishR01HL108599 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI YELON, DEBORAH · 2011 to 2019
$3.4M
Reconstruction of cardiovascular regulatory networks from large-scale single-cell analyses of cardiovascular lineagesR01HD085902 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C, YEO, EUGENE WEI-MING · 2016 to 2020
$3.1M
Rapid 3D bioprinting of biomimetic vascularized tissue constructsR01EB021857 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHEN, SHAOCHEN, DOKMECI, MEHMET REMZI · 2016 to 2019
$2.1M
Mechanisms of Ventricular Wall MorphogenesisR01HL141508 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C · 2018 to 2021
$1.9M
Regulatory Mechanisms of Cardiomyocyte Lineage SpecificationR01HL139709 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C · 2018 to 2021
$1.2M
NHLBI NIH HHS R01 HL108599NHLBI NIH HHS R01 HL139709NHLBI NIH HHS R01 HL141508NHLBI NIH HHS U01 HL131003NHLBI NIH HHS UM1 HL128773NIBIB NIH HHS R01 EB021857NICHD NIH HHS R01 HD085902
6 · The paper itself

Abstract

Pacemaker cardiomyocytes that create the sinoatrial node are essential for the initiation and maintenance of proper heart rhythm. However, illuminating developmental cues that direct their differentiation has remained particularly challenging due to the unclear cellular origins of these specialized cardiomyocytes. By discovering the origins of pacemaker cardiomyocytes, we reveal an evolutionarily conserved Wnt signaling mechanism that coordinates gene regulatory changes directing mesoderm cell fate decisions, which lead to the differentiation of pacemaker cardiomyocytes. We show that in zebrafish, pacemaker cardiomyocytes derive from a subset of Nkx2.5+ mesoderm that responds to canonical Wnt5b signaling to initiate the cardiac pacemaker program, including activation of pacemaker cell differentiation transcription factors Isl1 and Tbx18 and silencing of Nkx2.5. Moreover, applying these developmental findings to human pluripotent stem cells (hPSCs) notably results in the creation of hPSC-pacemaker cardiomyocytes, which successfully pace three-dimensional bioprinted hPSC-cardiomyocytes, thus providing potential strategies for biological cardiac pacemaker therapy.

Indexed as

Signal TransductionAnimalsBase SequenceBioprintingCell DifferentiationGene Expression Regulation, DevelopmentalHomeobox Protein Nkx-2.5HumansLoss of Function MutationMesodermModels, CardiovascularMyocytes, CardiacPluripotent Stem CellsStem CellsWnt ProteinsZebrafishHomeobox Protein Nkx-2.5Wnt Proteins3D bioprintingcanonical Wnt signalingdifferentiationhuman pluripotent stem cellspacemaker cardiomyocytesWnt5bzebrafish

Identifiers

PMID31402282
PMCPMC6759400
OpenAlexW2969165162

What OpenQuestion holds

Textmetadata
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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.