title: Adenosine signaling promotes hematopoietic stem and progenitor cell emergence.
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.
authors: Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA 02115 Harvard Stem Cell Institute, Howard Hughes Medical Institute, and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138.
authors: Lili
authors: L
authors: Jing
authors: Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA 02115 Harvard Stem Cell Institute, Howard Hughes Medical Institute, and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138.
authors: Owen J
authors: OJ
authors: Tamplin
authors: Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA 02115 Harvard Stem Cell Institute, Howard Hughes Medical Institute, and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138.
authors: Michael J
authors: MJ
authors: Chen
authors: Department of Medical Microbiology and Immunology and Department of Pediatrics, University of Wisconsin-Madison, Madison, WI 53706 Department of Medical Microbiology and Immunology and Department of Pediatrics, University of Wisconsin-Madison, Madison, WI 53706.
authors: Qing
authors: Q
authors: Deng
authors: Department of Medicine, Boston University School of Medicine and the Evans Center for Interdisciplinary Biomedical Research, Boston, MA 02118.
authors: Shenia
authors: S
authors: Patterson
authors: Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA 02115 Harvard Stem Cell Institute, Howard Hughes Medical Institute, and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 Harvard Stem Cell Institute, Howard Hughes Medical Institute, and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138.
authors: Peter G
authors: PG
authors: Kim
authors: Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA 02115 Harvard Stem Cell Institute, Howard Hughes Medical Institute, and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138.
authors: Ellen M
authors: EM
authors: Durand
authors: Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA 02115 Harvard Stem Cell Institute, Howard Hughes Medical Institute, and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138.
authors: Ashley
authors: A
authors: McNeil
authors: Department of Medical Microbiology and Immunology and Department of Pediatrics, University of Wisconsin-Madison, Madison, WI 53706 Department of Medical Microbiology and Immunology and Department of Pediatrics, University of Wisconsin-Madison, Madison, WI 53706.
authors: Julie M
authors: JM
authors: Green
authors: Department of Medicine, Boston University School of Medicine and the Evans Center for Interdisciplinary Biomedical Research, Boston, MA 02118.
authors: Shinobu
authors: S
authors: Matsuura
authors: Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA 02115 Harvard Stem Cell Institute, Howard Hughes Medical Institute, and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138.
authors: Julien
authors: J
authors: Ablain
authors: Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA 02115 Harvard Stem Cell Institute, Howard Hughes Medical Institute, and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138.
authors: Margot K
authors: MK
authors: Brandt
authors: Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA 02115 Harvard Stem Cell Institute, Howard Hughes Medical Institute, and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138.
authors: Thorsten M
authors: TM
authors: Schlaeger
authors: Department of Medical Microbiology and Immunology and Department of Pediatrics, University of Wisconsin-Madison, Madison, WI 53706 Department of Medical Microbiology and Immunology and Department of Pediatrics, University of Wisconsin-Madison, Madison, WI 53706.
authors: Anna
authors: A
authors: Huttenlocher
authors: Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA 02115 Harvard Stem Cell Institute, Howard Hughes Medical Institute, and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 Harvard Stem Cell Institute, Howard Hughes Medical Institute, and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138.
authors: George Q
authors: GQ
authors: Daley
authors: Department of Medicine, Boston University School of Medicine and the Evans Center for Interdisciplinary Biomedical Research, Boston, MA 02118.
authors: Katya
authors: K
authors: Ravid
authors: Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA 02115 Harvard Stem Cell Institute, Howard Hughes Medical Institute, and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 Harvard Stem Cell Institute, Howard Hughes Medical Institute, and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 Harvard Stem Cell Institute, Howard Hughes Medical Institute, and Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138 zon@enders.tch.harvard.edu.
authors: Leonard I
authors: LI
authors: Zon
mesh_terms: D000241:Adenosine / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism; D043704:Receptor, Adenosine A2B / Q000235:genetics / Q000378:metabolism*
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D043704:Receptor, Adenosine A2B; D000241:Adenosine