Royal College of Surgeons in Ireland
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Functional expression of the ATP-gated P2X7 receptor in human iPSC-derived astrocytes

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posted on 2023-07-28, 16:30 authored by Jaideep Cherakka KesavanJaideep Cherakka Kesavan, Orla Watters, Laura De Diego Garcia, Aida Menendez Mendez, Mariana AlvesMariana Alves, Klaus Dinkel, Michael Hamacher, Jochen PrehnJochen Prehn, David HenshallDavid Henshall, Tobias EngelTobias Engel

Activation of the ATP-gated P2X7 receptor (P2X7R), implicated in numerous diseases of the brain, can trigger diverse responses such as the release of pro-inflammatory cytokines, modulation of neurotransmission, cell proliferation or cell death. However, despite the known species-specific differences in its pharmacological properties, to date, most functional studies on P2X7R responses have been analyzed in cells from rodents or immortalised cell lines. To assess the endogenous and functional expression of P2X7Rs in human astrocytes, we differentiated human-induced pluripotent stem cells (hiPSCs) into GFAP and S100 β-expressing astrocytes. Immunostaining revealed prominent punctate P2X7R staining. P2X7R protein expression was also confirmed by Western blot. Importantly, stimulation with the potent non-selective P2X7R agonist 2',3'-O-(benzoyl-4-benzoyl)-adenosine 5'- triphosphate (BzATP) or endogenous agonist ATP induced robust calcium rises in hiPSC-derived astrocytes which were blocked by the selective P2X7R antagonists AFC-5128 or JNJ-47965567. Our findings provide evidence for the functional expression of P2X7Rs in hiPSC-derived astrocytes and support their in vitro utility in investigating the role of the P2X7R and drug screening in disorders of the central nervous system (CNS). 

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The original article is available at https://link.springer.com/

Published Citation

Kesavan J, et al. Functional expression of the ATP-gated P2X7 receptor in human iPSC-derived astrocytes. Purinergic Signal. 2023

Publication Date

15 July 2023

PubMed ID

37453017

Department/Unit

  • Physiology and Medical Physics
  • FutureNeuro Centre

Publisher

Springer Nature

Version

  • Published Version (Version of Record)