Evidence map›Paper›PMID 26755607›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Quantitative proteomics identify DAB2 as a cardiac developmental regulator that inhibits WNT/β-catenin signaling.

Peter Hofsteen, Aaron M Robitaille, Daniel Patrick Chapman, Randall T Moon, Charles E Murry

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
4.4field-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

26 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Genome Editing and Cardiac Regeneration.Advances in experimental medicine and biology · 2023
    Article
  10. Disabled-2 (International journal of molecular sciences · 2022
    Review
  11. Article
  12. The quest of cell surface markers for stem cell therapy.Cellular and molecular life sciences : CMLS · 2021
    Review
  13. Identification of the Lineage Markers and Inhibition ofInternational journal of molecular sciences · 2020
    Article
  14. Article
  15. Secretome Analysis Performed DuringFrontiers in cell and developmental biology · 2020
    Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article
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

5 authors at 2 institutions in 1 country.

Peter HofsteenDepartment of Pathology, University of Washington, Seattle, WA 98109; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109;
Aaron M RobitailleInstitute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109; Department of Pharmacology, University of Washington, Seattle, WA 98109;
Daniel Patrick ChapmanDepartment of Pathology, University of Washington, Seattle, WA 98109; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109;
Randall T MoonInstitute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109; Department of Pharmacology, University of Washington, Seattle, WA 98109; Howard Hughes Medical Institute, Chevy Chase, MD 20815; rtmoon@uw.edu murry@uw.edu.
Charles E MurryDepartment of Pathology, University of Washington, Seattle, WA 98109; Center for Cardiovascular Biology, University of Washington, Seattle, WA 98109; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109; Department of Bioengineering, University of Washington, Seattle, WA 98109; Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA 98109 rtmoon@uw.edu murry@uw.edu.
University of Washington · USCalifornia Institute for Regenerative Medicine · US

Funding

Washington National Primate Research CenterP51OD010425 · OD · UNIVERSITY OF WASHINGTON · PI Mari Ostendorf · 2012 to 2026
$201.8M
Self Renewal and Differentiation of Human Embryonic Stem CellsP01GM081619 · NIGMS · UNIVERSITY OF WASHINGTON · PI REH, THOMAS A · 2007 to 2017
$20.6M
Vascularization and Growth of Human Myocardial GraftsP01HL094374 · NHLBI · UNIVERSITY OF WASHINGTON · PI MINAMI, ELINA · 2010 to 2014
$14.5M
EXPERIMENTAL PATHOLOGY OF CARDIOVASCULAR DISEASET32HL007312 · NHLBI · UNIVERSITY OF WASHINGTON · PI MAJESKY, MARK W., SCHWARTZ, STEPHEN MARK · 1985 to 2019
$11.8M
Expansion of cardiac and hematopoietic progenitors by Wnt and NotchU01HL100405 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI EPSTEIN, JONATHAN A., MORRISEY, EDWARD E · 2009 to 2015
$8.1M
Cell-Based Cardiac RepairR01HL084642 · NHLBI · UNIVERSITY OF WASHINGTON · PI MURRY, CHARLES E · 2007 to 2014
$4.9M
Howard Hughes Medical InstituteNHLBI NIH HHS P01 HL094374NHLBI NIH HHS R01 HL084642NHLBI NIH HHS T32 HL007312NHLBI NIH HHS U01 HL100405NIGMS NIH HHS P01 GM081619NIH HHS P51 OD010425
6 · The paper itself

Abstract

To reveal the molecular mechanisms involved in cardiac lineage determination and differentiation, we quantified the proteome of human embryonic stem cells (hESCs), cardiac progenitor cells (CPCs), and cardiomyocytes during a time course of directed differentiation by label-free quantitative proteomics. This approach correctly identified known stage-specific markers of cardiomyocyte differentiation, including SRY-box2 (SOX2), GATA binding protein 4 (GATA4), and myosin heavy chain 6 (MYH6). This led us to determine whether our proteomic screen could reveal previously unidentified mediators of heart development. We identified Disabled 2 (DAB2) as one of the most dynamically expressed proteins in hESCs, CPCs, and cardiomyocytes. We used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) mutagenesis in zebrafish to assess whether DAB2 plays a functional role during cardiomyocyte differentiation. We found that deletion of Dab2 in zebrafish embryos led to a significant reduction in cardiomyocyte number and increased endogenous WNT/β-catenin signaling. Furthermore, the Dab2-deficient defects in cardiomyocyte number could be suppressed by overexpression of dickkopf 1 (DKK1), an inhibitor of WNT/β-catenin signaling. Thus, inhibition of WNT/β-catenin signaling by DAB2 is essential for establishing the correct number of cardiomyocytes in the developing heart. Our work demonstrates that quantifying the proteome of human stem cells can identify previously unknown developmental regulators.

Indexed as

ProteomicsAdaptor Proteins, Signal TransducingAnimalsApoptosis Regulatory Proteinsbeta CateninCell DifferentiationCells, CulturedEmbryonic Stem CellsFemaleHeartHumansIntercellular Signaling Peptides and ProteinsMyocytes, CardiacTumor Suppressor ProteinsWnt Signaling PathwayZebrafishAdaptor Proteins, Signal TransducingApoptosis Regulatory Proteinsbeta CateninCTNNB1 protein, humanDAB2 protein, humanDKK1 protein, humanIntercellular Signaling Peptides and ProteinsTumor Suppressor Proteinscardiomyocyteembryonic stem cellquantitative proteomicsWNT/β-cateninzebrafish

Identifiers

PMID26755607
PMCPMC4743825
OpenAlexW2239326726

What OpenQuestion holds

Textmetadata
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.