Retinoic Acid Signaling Is Essential for Embryonic Hematopoietic Stem Cell Development
Open accessAbstract
Hematopoietic stem cells (HSCs) develop from a specialized subpopulation of endothelial cells known as hemogenic endothelium (HE). Although the HE origin of HSCs is now well established in different species, the signaling pathways that control this transition remain poorly understood. Here, we show that activation of retinoic acid (RA) signaling in aorta-gonad-mesonephros-derived HE ex vivo dramatically enhanced its HSC potential, whereas conditional inactivation of the RA metabolizing enzyme retinal dehydrogenase 2 in VE-cadherin expressing endothelial cells in vivo abrogated HSC development. Wnt signaling completely blocked the HSC inductive effects of RA modulators, whereas inhibition of the pathway promoted the development of HSCs in the absence of RA signaling. Collectively, these findings position RA and Wnt signaling as key regulators of HSC development and in doing so provide molecular insights that will aid in developing strategies for their generation from pluripotent stem cells.
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Recent studies have highlighted the critical role of RA in the derivation of embryonic hematopoietic cells, lymphoid organs, and Langerhans cells that reside specifically in the epidermis.
“Besides the neurogenic potential of RA, recent studies have highlighted the critical role of RA in the derivation of embryonic hematopoietic cells9, lymphoid organs13, and Langerhans cells that reside specifically in the epidermis16.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [9]
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- Authors
- Chanda, B., Ditadi, A., Iscove, N. N., & Keller, G.
- Affiliations
- University of Toronto (CA)
- University Health Network (CA)
- Corresponding author
- Keller, Gordon
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 155
- Issue
- 1
- Pages
- 215-227
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1981379105
- Cited by
- 201
- References
- 56
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 15 · 2023: 17 · 2022: 16 · 2021: 12 · 2020: 11 · 2019: 14 · 2018: 18 · 2017: 12 · 2016: 28 · 2015: 21 · 2014: 18 · 2013: 1
- FWCI
- 16.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (MOP93569, FRN-72038762)
- National Heart, Lung, and Blood Institute (U01HL100405)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- retinoic acid signaling, hematopoietic stem cells, hemogenic endothelium, retinaldehyde dehydrogenase 2, Wnt signaling, aorta-gonad-mesonephros, endothelial-to-hematopoietic transition, VE-cadherin
- MeSH terms
- Aldehyde Oxidoreductases, Animals, Aorta, Embryo, Mammalian, Gonads, Hematopoietic Stem Cells, Mesonephros, Tretinoin, Down-Regulation, Receptors, Retinoic Acid, Mice, Wnt Signaling Pathway
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