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Cited by 339Congenital heart defects researchDevelopmental Biology and Gene RegulationMesenchymal stem cell research

Epicardial-Derived Cell Epithelial-to-Mesenchymal Transition and Fate Specification Require PDGF Receptor Signaling

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Smith, Christopher L., Baek, Seung Tae, Sung, Caroline Y., Tallquist, Michelle D.·2011·Circulation Research
DOI 10.1161/circresaha.110.235531PMC PMC3134964
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Abstract

Rationale: In early heart development, platelet-derived growth factor (PDGF) receptor expression in the heart ventricles is restricted to the epicardium. Previously, we showed that PDGFRβ is required for coronary vascular smooth muscle cell (cVSMC) development, but a role for PDGFRα has not been identified. Therefore, we investigated the combined and independent roles of these receptors in epicardial development. Objective: To understand the contribution of PDGF receptors in epicardial development and epicardial-derived cell fate determination. Methods and Results: By generating mice with epicardial-specific deletion of the PDGF receptors, we found that epicardial epithelial-to-mesenchymal transition (EMT) was defective. Sox9, an SRY-related transcription factor, was reduced in PDGF receptor-deficient epicardial cells, and overexpression of Sox9 restored epicardial migration, actin reorganization, and EMT gene expression profiles. The failure of epicardial EMT resulted in hearts that lacked epicardial-derived cardiac fibroblasts and cVSMC. Loss of PDGFRα resulted in a specific disruption of cardiac fibroblast development, whereas cVSMC development was unperturbed. Conclusions: Signaling through both PDGF receptors is necessary for epicardial EMT and formation of epicardial–mesenchymal derivatives. PDGF receptors also have independent functions in the development of specific epicardial-derived cell fates.

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  • The processes underlying AV EpiMT remain poorly characterized, as few studies assessing EpiMT focus on chamber epicardium.

    “However, the processes underlying AV EpiMT remain poorly characterized, as the few studies assessing EpiMT focus on chamber epicardium25–29.”

    From Cell diversity and plasticity during atrioventricular heart valve EMTs (2023) · cites this paper as [25]

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References 66 · Cited by 339

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Authors
Smith, C. L., Baek, S. T., Sung, C. Y., & Tallquist, M. D.
Affiliations
The University of Texas Southwestern Medical Center (US)
ORCID
Venue
Circulation Research
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2011-06-10
Volume
108
Issue
12
Pages
e15-26
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
DOI
10.1161/circresaha.110.235531
PMC
PMC3134964
OpenAlex
W2153560114
Cited by
339
References
66
Citations by year
2026: 13 · 2025: 19 · 2024: 21 · 2023: 15 · 2022: 24 · 2021: 23 · 2020: 24 · 2019: 24 · 2018: 22 · 2017: 29 · 2016: 38 · 2015: 16 · 2014: 17 · 2013: 31 · 2012: 19
FWCI
9.23
Type
journal article
Language
en
Open access
Locations
  • Circulation Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Open Access System for Information Sharing (Pohang University of Science and Technology) (submittedVersion)
Funders
  • American Heart Association
  • National Institutes of Health (5u01hl100401-07, NHLBI R01, HL-100401, HL074257)
  • National Heart, Lung, and Blood Institute (T32HL007360, HL100401, U01-HL-100401, HL074257, F30HL096277, R01HL074257)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
epicardium, epithelial-mesenchymal transition, PDGF receptor signaling, PDGFRA, PDGFRβ, SOX9, heart development
MeSH terms
Animals, Mice, Transgenic, Pericardium, Signal Transduction, Gene Expression Regulation, Developmental, Receptor, Platelet-Derived Growth Factor alpha, Receptor, Platelet-Derived Growth Factor beta, Mice, Sex-Determining Region Y Protein, SOX9 Transcription Factor, Epithelial-Mesenchymal Transition

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