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Cited by 1,019Congenital heart defects researchPluripotent Stem Cells ResearchMesenchymal stem cell research

Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart

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Zhou, Bin, Ma, Qing, Rajagopal, Satish, Wu, Sean M., Domian, Ibrahim, Rivera-Feliciano, José, Jiang, Dawei, von Gise, Alexander +3 more·2008·Nature
DOI 10.1038/nature07060PMC PMC2574791
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Abstract

The heart is formed from cardiogenic progenitors expressing the transcription factors Nkx2-5 and Isl1 (refs 1 and 2). These multipotent progenitors give rise to cardiomyocyte, smooth muscle and endothelial cells, the major lineages of the mature heart. Here we identify a novel cardiogenic precursor marked by expression of the transcription factor Wt1 and located within the epicardium-an epithelial sheet overlying the heart. During normal murine heart development, a subset of these Wt1(+) precursors differentiated into fully functional cardiomyocytes. Wt1(+) proepicardial cells arose from progenitors that express Nkx2-5 and Isl1, suggesting that they share a developmental origin with multipotent Nkx2-5(+) and Isl1(+) progenitors. These results identify Wt1(+) epicardial cells as previously unrecognized cardiomyocyte progenitors, and lay the foundation for future efforts to harness the cardiogenic potential of these progenitors for cardiac regeneration and repair.

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  • AV mesenchymal cells are also generated from the epicardium via EpiMT starting around E12.5.

    “AV mesenchymal cells are also generated from the epicardium via the epicardial-to-mesenchymal transition (EpiMT) starting around E12.5 (Fig. 1a).”

    From Cell diversity and plasticity during atrioventricular heart valve EMTs (2023) · cites this paper as [24]

    The passage labeled Abstract (page unavailable) says that some epicardial cells transition to a mesenchymal phenotype, and the References list a study of epicardium-derived cells in atrioventricular cushions. The cited paper does not itself establish that AV mesenchymal cells arise through this transition starting around E12.5. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Via EpiMT, epicardial cells contribute to smooth muscle cells, vasculature, pericytes, and fibroblasts, including those of the AVC and annulus fibrosus.

    “Via EpiMT, epicardial cells contribute to smooth muscle cells, vasculature, pericytes, and fibroblasts, including those of the atrioventricular canal (AVC) and the annulus fibrosus5,6,23,24.”

    From Cell diversity and plasticity during atrioventricular heart valve EMTs (2023) · cites this paper as [24]

    The passage on epicardial-cell fate (indexed as Abstract; page unavailable) says that a subset transitions to a mesenchymal phenotype and differentiates into smooth muscle and endothelial cells. That supports the EpiMT and vascular-cell portions of the claim, but our copy does not say these cells become pericytes or fibroblasts, including fibroblasts of the atrioventricular canal or annulus fibrosus. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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Cites

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Research works printed but not linked: 25

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Cited by

Sorted by citations

Authors
Zhou, B., Ma, Q., Rajagopal, S., Wu, S. M., Domian, I., Rivera-Feliciano, J., Jiang, D., von Gise, A., Ikeda, S., Chien, K. R., & Pu, W. T.
Affiliations
  • Boston Children's Hospital (US)
  • Harvard University (US)
Corresponding author
Pu, William T.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2008-06-22
Volume
454
Issue
7200
Pages
109-113
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature07060
PMC
PMC2574791
OpenAlex
W2098590189
Cited by
1,019
References
1
Citations by year
2026: 26 · 2025: 35 · 2024: 34 · 2023: 30 · 2022: 46 · 2021: 51 · 2020: 53 · 2019: 48 · 2018: 70 · 2017: 53 · 2016: 68 · 2015: 57 · 2014: 63 · 2013: 83 · 2012: 95
FWCI
28.28
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (P50HL074734)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
proepicardium, cardiomyocyte lineage, heart development, WT1, Tbx18, Nkx2.5, Isl1, cardiac progenitor cells, cardiac regeneration, cardiac repair, transcription factors
MeSH terms
Homeobox Protein Nkx-2.5, Animals, Cell Differentiation, Heart, Pericardium, Stem Cells, Transcription Factors, Homeodomain Proteins, Gene Expression Regulation, Developmental, Cell Lineage, WT1 Proteins, Myocytes, Cardiac, Green Fluorescent Proteins, Mice

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