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
  • Adenosine/genetics
  • Adenosine/metabolism*
  • Animals
  • Aorta/cytology
  • Aorta/metabolism*
  • Embryonic Stem Cells/cytology
  • Embryonic Stem Cells/metabolism
  • Endothelium, Vascular/cytology
  • Endothelium, Vascular/metabolism*
  • Hematopoietic Stem Cells/cytology
  • Hematopoietic Stem Cells/metabolism*
  • Humans
  • Interleukin-8/genetics
  • Interleukin-8/metabolism
  • Mice
  • Mice, Knockout
  • Multipotent Stem Cells/cytology
  • Multipotent Stem Cells/metabolism
  • Receptor, Adenosine A2B/genetics
  • Receptor, Adenosine A2B/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
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Errata and Notes