The P2X4 purinergic receptor has emerged as a potent regulator of hematopoietic stem/progenitor cell mobilization and homing-a novel view of P2X4 and P2X7 receptor interaction in orchestrating stem cell trafficking.
Animals
Chemotaxis
Female
Granulocyte Colony-Stimulating Factor
/ metabolism
Hematopoietic Stem Cell Mobilization
/ methods
Hematopoietic Stem Cell Transplantation
/ methods
Hematopoietic Stem Cells
/ cytology
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Purinergic P2X4
/ physiology
Receptors, Purinergic P2X7
/ genetics
Signal Transduction
Stem Cell Niche
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
15
06
2021
accepted:
12
07
2021
revised:
07
07
2021
pubmed:
22
7
2021
medline:
19
2
2022
entrez:
21
7
2021
Statut:
ppublish
Résumé
Recent evidence indicates that extracellular adenosine triphosphate (eATP), as a major mediator of purinergic signaling, plays an important role in regulating the mobilization and homing of hematopoietic stem progenitor cells (HSPCs). In our previous work we demonstrated that eATP activates the P2X7 ion channel receptor in HSPCs and that its deficiency impairs stem cell trafficking. To learn more about the role of the P2X purinergic receptor family in hematopoiesis, we phenotyped murine and human HSPCs with respect to the seven P2X receptors and observed that, these cells also highly express P2X4 receptors, which shows ~50% sequence similarity to P2X7 subtypes, but that P2X4 cells are more sensitive to eATP and signal much more rapidly. Using the selective P2X4 receptor antagonist PSB12054 as well as P2X4-KO mice, we found that the P2X4 receptor, similar to P2X7 receptor, promotes trafficking of HSPCs in that its deficiency leads to impaired chemotaxis of HSPCs in response to a stromal-derived factor 1 (SDF-1) gradient, less effective pharmacological mobilization, and defective homing and engraftment of HSPCs after transplantation into myeloablated hosts. This correlated with a decrease in SDF-1 expression in the BM microenvironment. Overall, our results confirm the proposed cooperative dependence of both receptors in response to eATP signaling. In G-CSF-induced mobilization, a lack of one receptor is not compensated by the presence of the other one, which supports their mutual dependence in regulating HSPC trafficking.
Identifiants
pubmed: 34285343
doi: 10.1038/s41375-021-01352-9
pii: 10.1038/s41375-021-01352-9
doi:
Substances chimiques
Receptors, Purinergic P2X4
0
Receptors, Purinergic P2X7
0
Granulocyte Colony-Stimulating Factor
143011-72-7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
248-256Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK074720
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL134644
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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