Cited by 186Pluripotent Stem Cells ResearchCongenital heart defects researchMesenchymal stem cell research

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Generation of the epicardial lineage from human pluripotent stem cells

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Witty, Alec D, Mihic, Anton, Tam, Roger Y, Fisher, Stephanie A, Mikryukov, Alexander, Shoichet, Molly S, Li, Ren-Ke, Kattman, Steven J, Keller, Gordon·2014·Nature Biotechnology

DOI 10.1038/nbt.3002PMC PMC4192149

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Abstract

The epicardium supports cardiomyocyte proliferation early in development and provides fibroblasts and vascular smooth muscle cells to the developing heart. The epicardium has been shown to play an important role during tissue remodeling after cardiac injury, making access to this cell lineage necessary for the study of regenerative medicine. Here we describe the generation of epicardial lineage cells from human pluripotent stem cells by stage-specific activation of the BMP and WNT signaling pathways. These cells display morphological characteristics and express markers of the epicardial lineage, including the transcription factors WT1 and TBX18 and the retinoic acid-producing enzyme ALDH1A2. When induced to undergo epithelial-to-mesenchymal transition, the cells give rise to populations that display characteristics of the fibroblast and vascular smooth muscle lineages. These findings identify BMP and WNT as key regulators of the epicardial lineage in vitro and provide a model for investigating epicardial function in human development and disease.

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Authors: Witty, A. D., Mihic, A., Tam, R. Y., Fisher, S. A., Mikryukov, A., Shoichet, M. S., Li, R.-K., Kattman, S. J., & Keller, G.
Affiliations: University Health Network (CA)
University of Toronto (CA)
Corresponding author: Keller, Gordon
ORCID: Tam, Roger Y
Mikryukov, Alexander
Shoichet, Molly S
Li, Ren-Ke
Keller, Gordon
Venue: Nature Biotechnology
Publisher: Springer Science and Business Media LLC
Published: 2014-09-21
Volume: 32
Issue: 10
Pages: 1026-1035
ISSN: 0733-222X (ISSN-L)
1087-0156
1546-1696
DOI: 10.1038/nbt.3002
PMC: PMC4192149
OpenAlex: W1969193847
Cited by: 180
References: 49
Citations by year: 2026: 6 · 2025: 8 · 2024: 11 · 2023: 12 · 2022: 10 · 2021: 20 · 2020: 20 · 2019: 23 · 2018: 13 · 2017: 19 · 2016: 21 · 2015: 16 · 2014: 1
FWCI: 7.79
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Biotechnology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Canadian Institutes of Health Research (MOP119507, MOP106538, 127793_1, MOP-84524)
National Heart, Lung, and Blood Institute (U01HL100405)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
Keywords: epicardium, human pluripotent stem cells, BMP signaling, Wnt signaling, WT1, Tbx18, ALDH1A2, epithelial-mesenchymal transition, cardiac fibroblasts, vascular smooth muscle cells, cardiac regeneration, heart development
MeSH terms: Aldehyde Dehydrogenase, Animals, Humans, Pericardium, Cell Lineage, Myocytes, Cardiac, Pluripotent Stem Cells, Mice, Bone Morphogenetic Protein 4, Epithelial-Mesenchymal Transition, Wnt Signaling Pathway

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Generation of the epicardial lineage from human pluripotent stem cells

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