PUBLICATION
Adenosine signaling promotes hematopoietic stem and progenitor cell emergence
- Authors
- Jing, L., Tamplin, O.J., Chen, M.J., Deng, Q., Patterson, S., Kim, P.G., Durand, E.M., McNeil, A., Green, J.M., Matsuura, S., Ablain, J., Brandt, M.K., Schlaeger, T.M., Huttenlocher, A., Daley, G.Q., Ravid, K., Zon, L.I.
- ID
- ZDB-PUB-150415-3
- Date
- 2015
- Source
- The Journal of experimental medicine 212(5): 649-63 (Journal)
- Registered Authors
- Huttenlocher, Anna, Jing, Lili, Schlaeger, Thorsten, Tamplin, Owen, Zon, Leonard I.
- Keywords
- none
- MeSH Terms
-
- Multipotent Stem Cells/cytology
- Multipotent Stem Cells/metabolism
- Mice, Knockout
- Embryonic Stem Cells/cytology
- Embryonic Stem Cells/metabolism
- PubMed
- 25870200 Full text @ J. Exp. Med.
Abstract
Hematopoietic stem cells (HSCs) emerge from aortic endothelium via the endothelial-to-hematopoietic transition (EHT). The molecular mechanisms that initiate and regulate EHT remain poorly understood. Here, we show that adenosine signaling regulates hematopoietic stem and progenitor cell (HSPC) development in zebrafish embryos. The adenosine receptor A2b is expressed in the vascular endothelium before HSPC emergence. Elevated adenosine levels increased runx1(+)/cmyb(+) HSPCs in the dorsal aorta, whereas blocking the adenosine pathway decreased HSPCs. Knockdown of A2b adenosine receptor disrupted scl(+) hemogenic vascular endothelium and the subsequent EHT process. A2b adenosine receptor activation induced CXCL8 via cAMP-protein kinase A (PKA) and mediated hematopoiesis. We further show that adenosine increased multipotent progenitors in a mouse embryonic stem cell colony-forming assay and in embryonic day 10.5 aorta-gonad-mesonephros explants. Our results demonstrate that adenosine signaling plays an evolutionary conserved role in the first steps of HSPC formation in vertebrates.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping