Abstract
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.
MeSH terms
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Adenosine Triphosphate / metabolism
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Adenosine Triphosphate / pharmacology*
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Animals
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Cell Cycle / drug effects*
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Cell Differentiation / drug effects
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Cell Proliferation / drug effects
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Chronic Disease
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Cytoplasmic Vesicles / drug effects
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Cytoplasmic Vesicles / metabolism
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Hematopoietic Stem Cells / cytology*
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Hematopoietic Stem Cells / drug effects*
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Hematopoietic Stem Cells / metabolism
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Inflammation / pathology
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Mice
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Myeloid Cells / cytology
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Myeloid Cells / drug effects
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Myeloid Cells / metabolism
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Purinergic P2X Receptor Antagonists / pharmacology
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Signal Transduction / drug effects
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Toll-Like Receptors / metabolism
Substances
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Purinergic P2X Receptor Antagonists
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Toll-Like Receptors
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Adenosine Triphosphate