Endoderm generates endothelial cells during liver development
Open accessAbstract
Organogenesis requires expansion of the embryonic vascular plexus that migrates into developing organs through a process called angiogenesis. Mesodermal progenitors are thought to derive endothelial cells (ECs) that contribute to both embryonic vasculogenesis and the subsequent organ angiogenesis. Here, we demonstrate that during development of the liver, which is an endoderm derivative, a subset of ECs is generated from FOXA2+ endoderm-derived fetal hepatoblast progenitor cells expressing KDR (VEGFR2/FLK-1). Using human and mouse embryonic stem cell models, we demonstrate that KDR+FOXA2+ endoderm cells developing in hepatic differentiation cultures generate functional ECs. This introduces the concept that ECs originate not exclusively from mesoderm but also from endoderm, supported in Foxa2 lineage-tracing mouse embryos by the identification of FOXA2+ cell-derived CD31+ ECs that integrate the vascular network of developing fetal livers.
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A proportion of HSECs may be derived from the endocardium and endoderm.
“though a proportion may be derived from the endocardium and endoderm”
From Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages (2020) · cites this paper as Goldman et al., 2014
The Discussion (page unavailable) reports that endoderm-derived progenitors contribute to a subpopulation of hepatic endothelial cells and suggests these may be fetal liver sinusoidal endothelial cells. Our copy does not identify the endocardium as a source of those cells, so only the endoderm part is supported. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThese findings support the model where the endoderm generates endothelial cells.
“These findings support the model where the endoderm generates endothelial cells”
From Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages (2020) · cites this paper as Goldman et al., 2014
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Additional file 1 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
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Additional file 5 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
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Additional file 13 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
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Additional file 11 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
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Additional file 6 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
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Additional file 9 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
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Additional file 4 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
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Additional file 2 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
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Additional file 7 of Single-nucleus transcriptome sequencing reveals hepatic cell atlas in pigs
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Griciunaite, M., Martinkus, J., Metikala, S., DeMoya, R. A., Gurung, S., Florat, D. R., & Sumanas, S. (2026) · eLife · doi:10.7554/elife.109406.1
Integrative vasculogenesis unifies distinct endothelial sources in the developing lungPreprint
Meziane, M., Litz, M. P. H., Chandrasekaran, P., Frank, D. B., & Li, P. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.08.723805
- Authors
- Goldman, O., Han, S., Hamou, W., Jodon de Villeroche, V., Uzan, G., Lickert, H., & Gouon-Evans, V.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Inserm (FR)
- Helmholtz Munich (DE)
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 3
- Issue
- 4
- Pages
- 556-565
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC4223703
- OpenAlex
- W2055458084
- Cited by
- 56
- References
- 22
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 3 · 2023: 7 · 2022: 3 · 2021: 6 · 2020: 6 · 2019: 2 · 2018: 6 · 2017: 3 · 2016: 3 · 2015: 5 · 2014: 1
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Site cant be reached (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK087867, R01DK133404)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- endothelial cell origin, endoderm, liver development, FOXA2, KDR, VEGFR2, angiogenesis, vasculogenesis, embryonic stem cells, hepatic differentiation, lineage tracing
- MeSH terms
- Animals, Cell Differentiation, Cell Line, Cells, Cultured, Endoderm, Humans, Liver, Mesoderm, Cell Lineage, Vascular Endothelial Growth Factor Receptor-2, Endothelial Cells, Mice, Hepatocyte Nuclear Factor 3-beta, Embryonic Stem Cells
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