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.


Journal

Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895

Informations de publication

Date de publication:
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

248-256

Subventions

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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Auteurs

Mateusz Adamiak (M)

Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
Department of Regenerative Medicine Medical University of Warsaw, Warsaw, Poland.

Kamila Bujko (K)

Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
Department of Regenerative Medicine Medical University of Warsaw, Warsaw, Poland.

Arjun Thapa (A)

Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.

Valentina Pensato (V)

Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.

Katarzyna Brzezniakiewicz-Janus (K)

Department of Hematology, University of Zielona Gora, Hospital Gorzow Wlkp., Zielona Gora, Poland.

Janina Ratajczak (J)

Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.

Daryl L Davies (DL)

Titus Family Department of Clinical Pharmacy, University of Southern California School of Pharmacy, Los Angeles, CA, USA.

Henning Ulrich (H)

Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.

Magda Kucia (M)

Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA. mjkuci01@louisville.edu.
Department of Regenerative Medicine Medical University of Warsaw, Warsaw, Poland. mjkuci01@louisville.edu.

Mariusz Z Ratajczak (MZ)

Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA. mzrata01@louisville.edu.
Department of Regenerative Medicine Medical University of Warsaw, Warsaw, Poland. mzrata01@louisville.edu.
Department of Hematology, University of Zielona Gora, Hospital Gorzow Wlkp., Zielona Gora, Poland. mzrata01@louisville.edu.

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