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Adenosine signaling promotes hematopoietic stem and progenitor cell emergence.

Jing L, Tamplin OJ, Chen MJ, Deng Q, Patterson S, Kim PG, Durand EM, McNeil A, Green JM, Matsuura S, Ablain J, Brandt MK, Schlaeger TM, Huttenlocher A, Daley GQ, Ravid K, Zon LI - J. Exp. Med. (2015)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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.

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Adenosine signaling through A2b specifically regulates HSPC development. (A–H) Control or A2b MO–injected embryos stained for runx1 in the AGM at 36 hpf (A and B), runx1/cmyb in the CHT at 60 hpf (C and D), cmyb in the CHT (E and F), and RAG1 in the thymus (red arrows in G and H) at 4.5 dpf. (I–X) Control or A2b MO–injected embryos stained for vasculature (flk1; I and J), dorsal aorta (ephrinB2; K and L), pronephros (cdh17; M and N), and somite (myoD; O and P), primitive hematopoiesis (gata1 and scl; Q–T), and cmyb and runx1 (U–X) at the developmental stages indicated. In I and J, red arrowheads mark intersegment staining. Bars, 100 µm.
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fig3: Adenosine signaling through A2b specifically regulates HSPC development. (A–H) Control or A2b MO–injected embryos stained for runx1 in the AGM at 36 hpf (A and B), runx1/cmyb in the CHT at 60 hpf (C and D), cmyb in the CHT (E and F), and RAG1 in the thymus (red arrows in G and H) at 4.5 dpf. (I–X) Control or A2b MO–injected embryos stained for vasculature (flk1; I and J), dorsal aorta (ephrinB2; K and L), pronephros (cdh17; M and N), and somite (myoD; O and P), primitive hematopoiesis (gata1 and scl; Q–T), and cmyb and runx1 (U–X) at the developmental stages indicated. In I and J, red arrowheads mark intersegment staining. Bars, 100 µm.

Mentions: Compared with cmyb, runx1 is more specifically expressed in nascent HSCs. We examined embryos using runx1 probe alone and found that knockdown of A2b strongly reduced runx1+ cells (Fig. 3, A and B). We also studied hematopoiesis and subsequent lineage differentiation at later time points after A2b inhibition. A2b morphants have reduced runx1+/cmyb+ HSPCs in the CHT at 60 hpf (Fig. 3, C and D), reduced cmyb+ multipotent progenitor cells in the CHT at 4.5 d postfertilization (dpf; Fig. 3, E and F), and reduced rag1+ thymic T cells (Fig. 3, G and H). Together, our results indicate that A2b regulates HSPC development.


Adenosine signaling promotes hematopoietic stem and progenitor cell emergence.

Jing L, Tamplin OJ, Chen MJ, Deng Q, Patterson S, Kim PG, Durand EM, McNeil A, Green JM, Matsuura S, Ablain J, Brandt MK, Schlaeger TM, Huttenlocher A, Daley GQ, Ravid K, Zon LI - J. Exp. Med. (2015)

Adenosine signaling through A2b specifically regulates HSPC development. (A–H) Control or A2b MO–injected embryos stained for runx1 in the AGM at 36 hpf (A and B), runx1/cmyb in the CHT at 60 hpf (C and D), cmyb in the CHT (E and F), and RAG1 in the thymus (red arrows in G and H) at 4.5 dpf. (I–X) Control or A2b MO–injected embryos stained for vasculature (flk1; I and J), dorsal aorta (ephrinB2; K and L), pronephros (cdh17; M and N), and somite (myoD; O and P), primitive hematopoiesis (gata1 and scl; Q–T), and cmyb and runx1 (U–X) at the developmental stages indicated. In I and J, red arrowheads mark intersegment staining. Bars, 100 µm.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4419349&req=5

fig3: Adenosine signaling through A2b specifically regulates HSPC development. (A–H) Control or A2b MO–injected embryos stained for runx1 in the AGM at 36 hpf (A and B), runx1/cmyb in the CHT at 60 hpf (C and D), cmyb in the CHT (E and F), and RAG1 in the thymus (red arrows in G and H) at 4.5 dpf. (I–X) Control or A2b MO–injected embryos stained for vasculature (flk1; I and J), dorsal aorta (ephrinB2; K and L), pronephros (cdh17; M and N), and somite (myoD; O and P), primitive hematopoiesis (gata1 and scl; Q–T), and cmyb and runx1 (U–X) at the developmental stages indicated. In I and J, red arrowheads mark intersegment staining. Bars, 100 µm.
Mentions: Compared with cmyb, runx1 is more specifically expressed in nascent HSCs. We examined embryos using runx1 probe alone and found that knockdown of A2b strongly reduced runx1+ cells (Fig. 3, A and B). We also studied hematopoiesis and subsequent lineage differentiation at later time points after A2b inhibition. A2b morphants have reduced runx1+/cmyb+ HSPCs in the CHT at 60 hpf (Fig. 3, C and D), reduced cmyb+ multipotent progenitor cells in the CHT at 4.5 d postfertilization (dpf; Fig. 3, E and F), and reduced rag1+ thymic T cells (Fig. 3, G and H). Together, our results indicate that A2b regulates HSPC development.

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: 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.

Show MeSH
Related in: MedlinePlus