Development of the hemangioblast defines the onset of hematopoiesis in human ES cell differentiation cultures
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The onset of hematopoiesis in the mouse embryo and in the embryonic stem (ES) cell differentiation model is defined by the emergence of the hemangioblast, a progenitor with both hematopoietic and vascular potential. While there is evidence for the existence of a hemangioblast in the mouse, it is unclear if this progenitor develops during the establishment of the human hematopoietic system. In this report, we have mapped hematopoietic development in human ES cell (hESC) differentiation cultures and demonstrated that a comparable hemangioblast population exists. The human hemangioblasts were identified by their capacity to generate blast colonies that display both hematopoietic and vascular potential. These colony-forming cells express the receptor tyrosine kinase KDR (VEGF receptor 2) and represent a transient population that develops in BMP-4-stimulated embryoid bodies (EBs) between 72 and 96 hours of differentiation, prior to the onset of the primitive erythroid program. Two distinct types of hemangioblasts were identified, those that give rise to primitive erythroid cells, macrophages, and endothelial cells and those that generate only the primitive erythroid population and endothelial cells. These findings demonstrate for the first time the existence of the human hemangioblast and in doing so identify the earliest stage of hematopoietic commitment.
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The protocol yields primitive iHPCs that are CD43+/CD235a+/CD41+ after 10 days.
“Our protocol (depicted in Figure 1Bi) yields primitive iHPCs that are CD43+/CD235a+/CD41+ after 10 days (Kennedy et al., 2007; Sturgeon et al., 2014).”
From iPSC-derived human microglia-like cells to study neurological diseases (2017) · cites this paper as Kennedy et al., 2007
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- Authors
- Kennedy, M., D'Souza, S. L., Lynch-Kattman, M., Schwantz, S., & Keller, G.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Department of Gene and Cell Medicine, The Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, NY
- ORCID
- Keller, Gordon
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2006-12-05
- Volume
- 109
- Issue
- 7
- Pages
- 2679-2687
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC1852226
- OpenAlex
- W1977120253
- Cited by
- 483
- References
- 55
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 11 · 2023: 18 · 2022: 34 · 2021: 23 · 2020: 14 · 2019: 20 · 2018: 19 · 2017: 20 · 2016: 24 · 2015: 36 · 2014: 25 · 2013: 27 · 2012: 37
- FWCI
- 17.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL080627)
- National Institute of General Medical Sciences (P20GM075019)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- hemangioblasts, hematopoiesis, human embryonic stem cells, hematopoietic progenitor cells, BMP4, embryoid bodies, macrophages, endothelial cells, hematopoietic differentiation
- MeSH terms
- Base Sequence, Cell Differentiation, Cell Line, Erythropoiesis, Hematopoiesis, Hematopoietic Stem Cells, Humans, Cytokines, DNA Primers, Gene Expression Regulation, Developmental, Platelet Endothelial Cell Adhesion Molecule-1, Bone Morphogenetic Proteins, Vascular Endothelial Growth Factor Receptor-2, Embryonic Stem Cells, Bone Morphogenetic Protein 4
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