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Adenosine signaling promotes hematopoietic stem and progenitor cell emergence

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) devel...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419349/
https://www.ncbi.nlm.nih.gov/pubmed/25870200
http://dx.doi.org/10.1084/jem.20141528
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author 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.
author_facet 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.
author_sort Jing, Lili
collection PubMed
description 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(2b) 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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spelling pubmed-44193492015-11-04 Adenosine signaling promotes hematopoietic stem and progenitor cell emergence 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. J Exp Med Article 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(2b) 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. The Rockefeller University Press 2015-05-04 /pmc/articles/PMC4419349/ /pubmed/25870200 http://dx.doi.org/10.1084/jem.20141528 Text en © 2015 Jing et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
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.
Adenosine signaling promotes hematopoietic stem and progenitor cell emergence
title Adenosine signaling promotes hematopoietic stem and progenitor cell emergence
title_full Adenosine signaling promotes hematopoietic stem and progenitor cell emergence
title_fullStr Adenosine signaling promotes hematopoietic stem and progenitor cell emergence
title_full_unstemmed Adenosine signaling promotes hematopoietic stem and progenitor cell emergence
title_short Adenosine signaling promotes hematopoietic stem and progenitor cell emergence
title_sort adenosine signaling promotes hematopoietic stem and progenitor cell emergence
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419349/
https://www.ncbi.nlm.nih.gov/pubmed/25870200
http://dx.doi.org/10.1084/jem.20141528
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