title: A novel role for P2X7 receptor signalling in the survival of mouse embryonic stem cells.
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.
authors: Department of Pharmacy and Pharmacology, University of Bath, Bath, UK.
authors: Belinda A N
authors: BA
authors: Thompson
authors: Michael P
authors: MP
authors: Storm
authors: James
authors: J
authors: Hewinson
authors: Sarah
authors: S
authors: Hogg
authors: Melanie J
authors: MJ
authors: Welham
authors: Amanda B
authors: AB
authors: MacKenzie
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D018408:Patch-Clamp Techniques; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D058486:Receptors, Purinergic P2X7 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D058920:Purinergic P2X Receptor Antagonists; D034741:RNA, Small Interfering; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate