Adenosine signaling promotes hematopoietic stem and progenitor cell emergence

作者：Jing Lili; Tamplin Owen J; Chen Michael J; Deng Qing; Patterson Shenia; Kim Peter G; Durand Ellen M; McNeil Ashley; Green Julie M; Matsuura Shinobu; Ablain Julien; Brandt Margot K; Schlaeger Thorsten M; Huttenlocher Anna; Daley George Q; Ravid Katya; Zon Leonard I^*

来源：Journal of Experimental Medicine, 2015, 212(5): 649-663.

DOI：10.1084/jem.20141528

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.

• 出版日期2015-5-4