The role of Ca²⁺ signaling on the self-renewal and neural differentiation of embryonic stem cells (ESCs)

Embryonic stem cells (ESCs) are promising resources for both scientific research and clinical regenerative medicine. With regards to the latter, ESCs are especially useful for treating several neurodegenerative disorders. Two significant characteristics of ESCs, which make them so valuable, are their capacity for self-renewal and their pluripotency, both of which are regulated by the integration of various signaling pathways. Intracellular Ca²⁺ signaling is involved in several of these pathways. It is known to be precisely controlled by different Ca²⁺ channels and pumps, which play an important role in a variety of cellular activities, including proliferation, differentiation and apoptosis. Here, we provide a review of the recent work conducted to investigate the function of Ca²⁺ signaling in the self-renewal and the neural differentiation of ESCs. Specifically, we describe the role of intracellular Ca²⁺ mobilization mediated by RyRs (ryanodine receptors); by cADPR (cyclic adenosine 5'-diphosphate ribose) and CD38 (cluster of differentiation 38/cADPR hydrolase); and by NAADP (nicotinic acid adenine dinucleotide phosphate) and TPC2 (two pore channel 2). We also discuss the Ca²⁺ influx mediated by SOCs (store-operated Ca²⁺ channels), TRPCs (transient receptor potential cation channels) and LTCC (L-type Ca²⁺ channels) in the pluripotent ESCs as well as in neural differentiation of ESCs. Moreover, we describe the integration of Ca²⁺ signaling in the other signaling pathways that are known to regulate the fate of ESCs.