Hao Baixia, Webb Sarah E, Miller Andrew L, Yue Jianbo
Division of Life Science and State Key Laboratory of Molecular Neuroscience, HKUST, Clear Water Bay, Hong Kong, China.
Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong, China.
Cell Calcium. 2016 Mar;59(2-3):67-74. doi: 10.1016/j.ceca.2016.01.004. Epub 2016 Feb 27.
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 Ca(2+) signaling is involved in several of these pathways. It is known to be precisely controlled by different Ca(2+) 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 Ca(2+) signaling in the self-renewal and the neural differentiation of ESCs. Specifically, we describe the role of intracellular Ca(2+) 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 Ca(2+) influx mediated by SOCs (store-operated Ca(2+) channels), TRPCs (transient receptor potential cation channels) and LTCC (L-type Ca(2+) channels) in the pluripotent ESCs as well as in neural differentiation of ESCs. Moreover, we describe the integration of Ca(2+) signaling in the other signaling pathways that are known to regulate the fate of ESCs.
胚胎干细胞（ESCs）是科学研究和临床再生医学中很有前景的资源。就后者而言，胚胎干细胞对于治疗多种神经退行性疾病特别有用。胚胎干细胞的两个显著特征使其如此有价值，即自我更新能力和多能性，这两者都由各种信号通路的整合来调节。细胞内Ca(2+)信号传导参与其中一些通路。已知它受到不同的Ca(2+)通道和泵的精确控制，这些通道和泵在包括增殖、分化和凋亡在内的各种细胞活动中起重要作用。在这里，我们综述了最近为研究Ca(2+)信号在胚胎干细胞自我更新和神经分化中的功能而开展的工作。具体而言，我们描述了由兰尼碱受体（RyRs）介导的细胞内Ca(2+)动员的作用；由环腺苷5'-二磷酸核糖（cADPR）和分化簇38/环腺苷5'-二磷酸核糖水解酶（CD38）介导的作用；以及由烟酰胺腺嘌呤二核苷酸磷酸（NAADP）和双孔通道2（TPC2）介导的作用。我们还讨论了在多能胚胎干细胞以及胚胎干细胞神经分化过程中，由储存操纵性Ca(2+)通道（SOCs）、瞬时受体电位阳离子通道（TRPCs）和L型Ca(2+)通道（LTCC）介导的Ca(2+)内流。此外，我们描述了Ca(2+)信号在已知调节胚胎干细胞命运的其他信号通路中的整合。
