Evidence map›Paper›PMID 40343798›Full record

ArticleCell reports2025

A retinoic acid:YAP1 signaling axis controls atrial lineage commitment.

Elizabeth Abraham, Aleksandra Kostina, Brett Volmert, Thomas Roule, Ling Huang, Jingting Yu, April E Williams, Emily Megill, Aidan Douglas, Olivia M Pericak and 9 more

Abstract read
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Elucidating Gene Functions in Congenital Heart Disease.Current treatment options in cardiovascular medicine · 2026
    Review
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Elizabeth AbrahamDepartment of Cardiovascular Sciences, Aging + Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Aleksandra KostinaInstitute for Quantitative Health Science and Engineering, Division of Developmental and Stem Cell Biology, Michigan State University, East Lansing, MI 48824, USA; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI 48824, USA.
Brett VolmertInstitute for Quantitative Health Science and Engineering, Division of Developmental and Stem Cell Biology, Michigan State University, East Lansing, MI 48824, USA; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI 48824, USA.
Thomas RouleRaymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Ling HuangIntegrative Genomics and Bioinformatics Core, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Jingting YuIntegrative Genomics and Bioinformatics Core, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
April E WilliamsIntegrative Genomics and Bioinformatics Core, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Emily MegillDepartment of Cardiovascular Sciences, Aging + Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Aidan DouglasDepartment of Cardiovascular Sciences, Aging + Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Olivia M PericakDepartment of Cardiovascular Sciences, Aging + Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Alex MorrisCancer Epigenetics Institute, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Eleonora StronatiDepartment of Child and Adolescence Psychiatry, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Arantza Larrinaga-ZamanilloDepartment of Cardiovascular Sciences, Aging + Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Raquel FueyoDepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Mikel ZubillagaDepartment of Cardiovascular Sciences, Aging + Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Mark D AndrakeMolecular Modeling Facility, Program in Cancer Signaling and Microenvironment, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Naiara AkizuRaymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Aitor AguirreInstitute for Quantitative Health Science and Engineering, Division of Developmental and Stem Cell Biology, Michigan State University, East Lansing, MI 48824, USA; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI 48824, USA.
Conchi EstarasDepartment of Cardiovascular Sciences, Aging + Cardiovascular Discovery Center, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA; Cancer Epigenetics Institute, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. Electronic address: conchi.estaras@temple.edu.

Funding

WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Eric Andrew Ross · 1985 to 2026
$138.8M
Integrative Cardiovascular PathophysiologyT32HL091804 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI ELROD, JOHN WILLIAM · 2008 to 2024
$4.5M
Oxylipin Signaling in Congenital Heart DiseaseR01HL151505 · NHLBI · MICHIGAN STATE UNIVERSITY · PI AGUIRRE, AITOR · 2021 to 2025
$2.2M
The Role of Hippo-Yap1 Signaling in Germ-layer SpecificationR01HD106969 · NICHD · TEMPLE UNIV OF THE COMMONWEALTH · PI Concepcion Estaras · 2022 to 2026
$2.1M
Lipid signaling in cardiac development and diseaseK01HL135464 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AGUIRRE, AITOR · 2017 to 2021
$795k
The Role of YAP1:TEAD Enhancers in the Retinoic Acid-Regulatory Network of Cardiac ProgenitorsR56HL163146 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI ESTARAS, CONCEPCION · 2022 to 2022
$469k
Investigating the role of YAP1 in blood cell specificationF31HD113419 · NICHD · TEMPLE UNIV OF THE COMMONWEALTH · PI ABRAHAM, ELIZABETH · 2024 to 2025
$47k
NCI NIH HHS P30 CA006927NHLBI NIH HHS K01 HL135464NHLBI NIH HHS R01 HL151505NHLBI NIH HHS R56 HL163146NHLBI NIH HHS T32 HL091804NICHD NIH HHS F31 HD113419NICHD NIH HHS R01 HD106969
6 · The paper itself

Abstract

In cardiac progenitor cells (CPCs), retinoic acid (RA) signaling induces atrial lineage gene expression and acquisition of an atrial cell fate. To achieve this, RA coordinates a complex regulatory network of downstream effectors that is not fully identified. To address this gap, we applied a functional genomics approach (i.e., scRNA-seq and snATAC-seq) to untreated and RA-treated human embryonic stem cell (hESC)-derived CPCs. Unbiased analysis revealed that the Hippo effectors YAP1 and TEAD4 are integrated with the atrial transcription factor enhancer network and that YAP1 activates RA enhancers in CPCs. Furthermore, Yap1 deletion in mouse embryos compromises the expression of RA-induced genes, such as Nr2f2, in the CPCs of the second heart field. Accordingly, in hESC-derived patterned heart organoids, YAP1 regulates the formation of an atrial chamber but is dispensable for the formation of a ventricle. Overall, our findings revealed that YAP1 cooperates with RA signaling to induce atrial lineages during cardiogenesis.

Indexed as

Adaptor Proteins, Signal TransducingCell LineageHeart AtriaSignal TransductionTretinoinAnimalsCell Cycle ProteinsCell DifferentiationDNA-Binding ProteinsHuman Embryonic Stem CellsHumansMiceMuscle ProteinsTEA Domain Transcription FactorsTranscription FactorsYAP-Signaling ProteinsAdaptor Proteins, Signal TransducingCell Cycle ProteinsDNA-Binding ProteinsMuscle ProteinsTEA Domain Transcription FactorsTranscription FactorsTretinoinYAP1 protein, humanYap1 protein, mouseYAP-Signaling Proteinsatrial differentiationcardiac enhancerscardiac progenitorschamber developmentCP: Developmental biologyheart organoidsNR2F2retinoic acid signalingSHFTEAD4YAP1

Identifiers

PMID40343798
PMCPMC12186250

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.