Evidence map›Paper›PMID 39866065›Full record

ArticleDevelopment (Cambridge, England)2025

Dynamic map illuminates Hippo-cMyc module crosstalk driving cardiomyocyte proliferation.

Bryana N Harris, Laura A Woo, R Noah Perry, Alexia M Wallace, Mete Civelek, Matthew J Wolf, Jeffrey J Saucerman

Abstract read
In one paragraph

Article in Development (Cambridge, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Advances in Drug Discovery for Cardiomyocyte Proliferation.Current treatment options in cardiovascular medicine · 2025
    Review
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

7 authors.

Bryana N HarrisDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908-0759, USA.
Laura A WooDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908-0759, USA.
R Noah PerryDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908-0759, USA.ORCID 0000-0002-3555-0964
Alexia M WallaceDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908-0759, USA.
Mete CivelekDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908-0759, USA.
Matthew J WolfRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908-0759, USA.
Jeffrey J SaucermanDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908-0759, USA.ORCID 0000-0001-9464-8374

Funding

Systems Pharmacology Model of Cardiac HypertrophyR01HL162925 · NHLBI · UNIVERSITY OF VIRGINIA · PI SAUCERMAN, JEFFREY J., WOLF, MATTHEW J · 2022 to 2025
$3.1M
Computational and Experimental Modeling of Cardiomyocyte ProliferationR01HL160665 · NHLBI · UNIVERSITY OF VIRGINIA · PI SAUCERMAN, JEFFREY J., VAN BERLO, JOHANNES (JOP) · 2022 to 2025
$2.8M
DYRK1a as a therapeutic target to treat myocardial infarctionR01HL158718 · NHLBI · UNIVERSITY OF VIRGINIA · PI WOLF, MATTHEW J · 2021 to 2024
$1.6M
National Science FoundationNHLBI NIH HHS R01 HL158718NHLBI NIH HHS R01 HL160665NHLBI NIH HHS R01 HL162925NIH HHS R01HL162925
6 · The paper itself

Abstract

Numerous regulators of cardiomyocyte (CM) proliferation have been identified, yet how they coordinate during cardiac development or regeneration is poorly understood. Here, we developed a computational model of the CM proliferation regulatory network to obtain key regulators and systems-level understanding. The model defines five modules (DNA replication, mitosis, cytokinesis, growth factor, Hippo pathway) and integrates them into a network of 72 nodes and 88 reactions that correctly predicts 74 of 81 (91.35%) independent experiments from the literature. The model predicts that in response to YAP activation, the Hippo module crosstalks to the growth factor module via PI3K and cMyc to drive cell cycle activity. This predicted YAP-cMyc axis is validated experimentally in rat CMs and further supported by YAP-stimulated cMyc open chromatin and mRNA in mouse hearts. This validated computational model predicts how individual regulators and modules coordinate to control CM proliferation.

Indexed as

Cell ProliferationMyocytes, CardiacProtein Serine-Threonine KinasesAnimalsComputer SimulationHippo Signaling PathwayMiceModels, BiologicalRatsSignal TransductionYAP-Signaling ProteinsProtein Serine-Threonine KinasesYap1 protein, mouseYAP-Signaling ProteinsCardiomyocyte proliferationRegenerationSystems biology

Identifiers

PMID39866065
PMCPMC11883243

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.