A novel role for P2X7 receptor signalling in the survival of mouse embryonic stem cells

Belinda A N Thompson, Michael P Storm, J Hewinson, Sarah Hogg, Melanie J Welham, Amanda B Mackenzie

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The growth of a pluripotent embryonic stem (ES) cell population is dependent on cell survival, proliferation and self-renewal. The nucleotide ATP represents an important extracellular signalling molecule that regulates the survival of differentiated cells, however, its role is largely undefined in embryonic stem cells. Here we report a role for ATP-gated P2X7 receptors in ES cell survival. The functional expression of P2X7 receptors in undifferentiated mouse ES cells is demonstrated using a selective P2X7 antagonist and small interfering RNA knockdown of these receptors. Our data illustrate a key role for the P2X7 receptor as an essential pro-survival signal required for optimal ES cell colony growth in the presence of leukemia inhibitor factor (LIF). However, chronic exposure to exogenous ATP leads to rapid P2X7-dependent cell death via necrosis. Together, these data demonstrate a novel role for P2X7 receptors in regulation of ES cell behaviour where they can mediate either a pro-survival or pro-death signal depending on the mode of activation.
Original languageEnglish
Pages (from-to)770-778
Number of pages9
JournalCellular Signalling
Volume24
Issue number3
Early online date18 Nov 2011
DOIs
Publication statusPublished - Mar 2012

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