期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 212, 期 5, 页码 649-663出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20141528
关键词
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资金
- National Heart, Lung, and Blood Institute (NHLBI) [R01 HL04880-21, P015P01HL32262-32, 5U01 HL10001-05, HL93149]
- National Institute of Diabetes and Digestive and Kidney Diseases [5P30 DK49216, R24 DK092760, 5R01 DK53298]
- Howard Hughes Medical Institute
- NHLBI [HL007969]
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 A(2)b 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 A(2b) adenosine receptor disrupted scl(+) hemogenic vascular endothelium and the subsequent EHT process. A(2b) 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.
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