Journal
CELL DEATH AND DIFFERENTIATION
Volume 18, Issue 3, Pages 396-404Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2010.107
Keywords
hematopoietic stem cell; ATP; cell cycle; purinergic receptors; inflammation
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Funding
- Swiss National Science Foundation
- Fondazione Ticinese per la Ricerca sul Cancro
- Fondazione per la Ricerca sulla Trasfusione e sui Trapianti
- European School of Oncology Foundation
- G.G.G. Foundation
- European Union [MUGEN LSHB-CT-2005-005203]
- Fondazione Stella Major
- Swiss Cancer League/Oncosuisse
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Extracellular nucleotides regulate many cellular functions through activation of purinergic receptors in the plasma membrane. Here, we show that in hematopoietic stem cell (HSC), ATP is stored in vesicles and released in a calcium-sensitive manner. HSC expresses ATP responsive P2X receptors and in vitro pharmacological P2X antagonism restrained hematopoietic progenitors proliferation, but not myeloid differentiation. In mice suffering from chronic inflammation, HSCs were significantly expanded and their cycling activity was sensitive to treatment with the P2X antagonist periodate-oxidized 2,3-dialdehyde ATP. Our results indicate that ATP acts as an autocrine stimulus in regulating HSCs pool size. Cell Death and Differentiation (2011) 18, 396-404; doi:10.1038/cdd.2010.107; published online 27 August 2010
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