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Generation of the epicardial lineage from human pluripotent stem cells
Open accessAbstract
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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“The derivation of CMs can be achieved by controlling the expression of Wnt and BMP at specific times from the mesoderm stage [397,398].”
From Cardiovascular disease models: A game changing paradigm in drug discovery and screening (2019) · cites this paper as [397]
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“We believe enhanced differentiation at lower CHIR concentrations can be attributed to endogenous morphogen production due to the self-assembling conditions provided28–32.”
From Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease (2021) · cites this paper as [28]
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Metadata
- 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
- Venue
- Nature Biotechnology
- Published
- 2014-09-21
- Volume
- 32
- Issue
- 10
- Pages
- 1026-1035
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- 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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