Cell-autonomous regulation of hematopoietic stem cell cycling activity by ATP.
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.
Casati
A
A
Institute for Research in Biomedicine, Bellinzona CH-6500, Switzerland. fabio.grassi@irb.unisi.ch
Frascoli
M
M
Traggiai
E
E
Proietti
M
M
Schenk
U
U
Grassi
F
F
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002908:Chronic Disease; D022162:Cytoplasmic Vesicles / Q000187:drug effects / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051193:Toll-Like Receptors / Q000378:metabolism
D058920:Purinergic P2X Receptor Antagonists; D051193:Toll-Like Receptors; D000255:Adenosine Triphosphate
Cell. 2008 Dec 12;135(6):1118-29
19062086
Cell. 2005 Jul 1;121(7):1109-21
15989959
Nature. 2003 Oct 23;425(6960):836-41
14574412
Mol Pharmacol. 1995 Aug;48(2):178-83
7544432
Ann N Y Acad Sci. 2007 Jun;1106:41-53
17332071
J Biol Chem. 1993 Apr 15;268(11):8199-203
8463330
Nat Immunol. 2006 Jul;7(7):732-9
16751774
J Exp Med. 2001 May 7;193(9):1005-14
11342585
J Neurosci. 2008 Apr 30;28(18):4702-11
18448647
J Cardiovasc Pharmacol. 1996 Jun;27(6):872-5
8761855
Nat Rev Immunol. 2003 Jul;3(7):521-33
12876555
J Biol Chem. 2002 Nov 22;277(47):44638-50
12244041
Nature. 2003 Oct 23;425(6960):841-6
14574413
J Exp Med. 2006 Feb 20;203(2):461-71
16492806
Am J Physiol Cell Physiol. 2007 Oct;293(4):C1420-5
17699635
Proc Natl Acad Sci U S A. 2006 May 16;103(20):7655-9
16682648
J Clin Invest. 2006 Oct;116(10):2808-16
17016561
Annu Rev Physiol. 2009;71:333-59
18851707
Br J Pharmacol. 1991 May;103(1):1203-5
1652343
Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6465-70
20308565
Nat Med. 2009 Jun;15(6):696-700
19483695
Cell. 2000 Jan 7;100(1):157-68
10647940
Stem Cells. 2008 Jul;26(7):1778-86
18483422
Nature. 2009 Apr 16;458(7240):904-8
19212321
Blood. 2009 Feb 5;113(6):1250-6
18945958
Cell. 1997 Nov 28;91(5):661-72
9393859
Thromb Haemost. 2010 Feb;103(2):398-407
20024498
J Exp Med. 2005 Jun 6;201(11):1771-80
15939792
Science. 1996 Jul 12;273(5272):242-5
8662508
Nature. 2009 Jun 25;459(7250):1131-5
19440194
Novartis Found Symp. 2006;276:26-48; discussion 48-57, 275-81
16805422
J Neurosci. 2010 Jan 13;30(2):573-82
20071520
Sci Signal. 2010 Jan 12;3(104):re1
20068232
Physiology (Bethesda). 2005 Oct;20:349-56
16174874
Blood. 2004 May 1;103(9):3258-64
14726388
J Pharmacol Exp Ther. 2008 Feb;324(2):409-15
18042830
Neuropharmacology. 2005 Mar;48(3):461-8
15721178
J Pharmacol Exp Ther. 1990 Mar;252(3):1060-7
2319458
Immunity. 2006 Jun;24(6):801-812
16782035
Nat Med. 2004 Jan;10(1):64-71
14702636
Cell. 2004 Jul 23;118(2):149-61
15260986
J Immunol. 2003 Apr 15;170(8):3939-43
12682220
Nature. 2001 Nov 1;414(6859):105-11
11689955
Blood. 2004 Sep 15;104(6):1662-70
15161674
J Biol Chem. 2003 Jan 10;278(2):1354-62
12414798
EMBO J. 2006 Aug 9;25(15):3515-23
16858398