Wnt signaling controls the specification of definitive and primitive hematopoiesis from human pluripotent stem cells
Open accessAbstract
Efforts to derive hematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) are complicated by the fact that embryonic hematopoiesis consists of two programs, primitive and definitive, that differ in developmental potential. As only definitive hematopoiesis generates HSCs, understanding how this program develops is essential for being able to produce this cell population in vitro. Here we show that both hematopoietic programs transition through hemogenic endothelial intermediates and develop from KDR(+)CD34(-)CD144(-) progenitors that are distinguished by CD235a expression. Generation of primitive progenitors (KDR(+)CD235a(+)) depends on stage-specific activin-nodal signaling and inhibition of the Wnt-β-catenin pathway, whereas specification of definitive progenitors (KDR(+)CD235a(-)) requires Wnt-β-catenin signaling during this same time frame. Together, these findings establish simple selective differentiation strategies for the generation of primitive or definitive hematopoietic progenitors by Wnt-β-catenin manipulation, and in doing so provide access to enriched populations for future studies on hPSC-derived hematopoietic development.
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The marker expression pattern is consistent with these cells representing in vitro counterparts of early haemogenic endothelia.
“This immuno-histochemical panel is consistent with these cells representing the in vitro counterparts of early haemogenic endothelia 20.”
From Efficient derivation of microglia-like cells from human pluripotent stem cells (2016) · cites this paper as [20]
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 Sturgeon et al., 2014
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- Authors
- Sturgeon, C. M., Ditadi, A., Awong, G., Kennedy, M., & Keller, G.
- Affiliations
- University Health Network (CA)
- Corresponding author
- Keller, Gordon
- Venue
- Nature Biotechnology
- Published
- 2014-05-18
- Volume
- 32
- Issue
- 6
- Pages
- 554-561
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC4152856
- OpenAlex
- W2011687861
- Cited by
- 467
- References
- 44
- Citations by year
- 2026: 20 · 2025: 24 · 2024: 55 · 2023: 38 · 2022: 55 · 2021: 44 · 2020: 47 · 2019: 34 · 2018: 32 · 2017: 37 · 2016: 44 · 2015: 30 · 2014: 7
- FWCI
- 16.14
- 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
- Hospital for Sick Children
- National Institutes of Health
- U.S. Public Health Service (MOP12927, HOP83070, MOP93569)
- Canadian Institutes of Health Research
- National Heart, Lung, and Blood Institute (U01HL100395)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- Wnt signaling, β-catenin, definitive hematopoiesis, primitive hematopoiesis, human pluripotent stem cells, hematopoietic stem cells, hemogenic endothelium, glycophorin A, Activin/Nodal signaling, embryonic hematopoiesis
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Hematopoiesis, Hematopoietic Stem Cells, Humans, Pluripotent Stem Cells, Mice, Wnt Signaling Pathway
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