Coupling switch of P2Y-IP3 receptors mediates differential Ca~(2+)-signaling in human embryonic stem cells and derived cardiovascular progenitor cells

Purinergic signaling mediated by P2 receptors(P2Rs) plays important roles in embryonic and stem cell development. However, how it mediates Ca~(2+) signals in human embryonic stem cells(h ESCs) and derived cardiovascular progenitor cells(CVPCs) remains unclear. Here, we determined the role of P2 Rs in mediating Ca~(2+) mobilizations of these cells. IP3R3 knockdown(KD) or IP3R2 knockout(KO) h ESCs were established by sh RNA-or TALEN-mediated gene manipulations, respectively. Confocal imaging revealed that Ca~(2+) responses in CVPCs to ATP and UTP were more sensitive and stronger than those in h ESCs. Consistently, the gene expression levels of most P2 YRs except P2Y1 were increased in CVPCs. Suramin or PPADS blocked ATP-induced Ca~(2+) transients in h ESCs but only partially inhibited those in CVPCs. Moreover, the P2Y1 receptor-specific antagonist MRS2279 abolished most ATP-induced Ca~(2+) signals in h ESCs but not in CVPCs. P2Y1 receptor-specific agonist MRS2365 induced Ca~(2+) transients only in h ESCs but no...Purinergic signaling mediated by P2 receptors(P2Rs) plays important roles in embryonic and stem cell development. However, how it mediates Ca~(2+) signals in human embryonic stem cells(h ESCs) and derived cardiovascular progenitor cells(CVPCs) remains unclear. Here, we determined the role of P2 Rs in mediating Ca~(2+) mobilizations of these cells. IP3R3 knockdown(KD) or IP3R2 knockout(KO) h ESCs were established by sh RNA-or TALEN-mediated gene manipulations, respectively. Confocal imaging revealed that Ca中国生物物理学会神经生物物理与神经信息学专业委员会