胚胎干细胞（embryonic stem cells, ESCs）自我更新和分化命运的决定受胞内外信号分子共同精细地调控。钙信号对细胞的多种生理活动，例如细胞的增殖、凋亡和分化都具有重要的调控作用。内质网三磷酸肌醇.受体（IP3R）是胞内重要的钙离子释放受体，在ESCs中存在着三种IP3R亚型，但它们在胚胎干细胞中的作用并不清楚。
1月15日， Cell Death and Differentiation杂志在线发表了中国科学院上海生命科学研究院/上海交通大学医学院健康科学研究所杨黄恬研究组的最新研究工作“Type 3 inositol 1,4,5-trisphosphate receptor negatively regulates apoptosis during mouse embryonic stem cell differentiation”。以往人们一般认为IP3R3介导的钙信号是一种促凋亡因子。博士研究生梁冀和其他研究组成员在杨黄恬研究员的指导下证明在胚胎干细胞早期分化过程中IP3R3介导的钙信号发挥着抗凋亡作用，IP3R3通过控制早期胚层细胞的凋亡在胚胎干细胞的中胚层和部分内胚层分化命运的决定中发挥着重要的调控作用。这一研究发现丰富了对IP3R调控的钙信号参与胚胎干细胞分化命运决定的认识，揭示了胚胎干细胞分化过程中的凋亡活动与胚层分化命运决定之间的关联和其调控新机制。
生物谷推荐原始出处：
Cell Death and Differentiation advance online publication 15 January 2010; doi: 10.1038/cdd.2009.209
Type 3 inositol 1,4,5-trisphosphate receptor negatively regulates apoptosis during mouse embryonic stem cell differentiation
Edited by V De Laurenzi
J Liang1, Y-J Wang1, Y Tang1, N Cao1, J Wang1 and H-T Yang1,2,3
1Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) and Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China
2Laboratory of Molecular Cardiology of Shanghai Stem Cell Institute, SJTUSM, Shanghai, China
3Shanghai Key Laboratory of Vascular Biology, Ruijin Hospital, SJTUSM, Shanghai, China
Ca2+ signals generated by inositol 1,4,5-trisphosphate receptors (IP3Rs) are crucial for cellular processes such as apoptosis and differentiation. However, the exact roles of IP3Rs and their contributions to Ca2+ signals in pluripotent embryonic stem (ES) cell behaviors remain largely unknown. In this study, we showed that the expression of type 3 IP3R (IP3R3) was transiently downregulated with a concomitant increase in apoptosis at the early differentiation stage of murine ES cells. Knockdown of IP3R3 by small interfering RNA increased apoptosis in differentiating cells but not in undifferentiated ES cells. Moreover, IP3R3 overexpression had the opposite effect. Consistently, IP3R3 knockdown altered Ca2+ oscillations in differentiating cells but not in undifferentiated ES cells. The apoptosis in differentiating IP3R3-knockdown cells was decreased by chelating intracellular Ca2+ with BAPTA-AM and increased in control ones. Furthermore, IP3R3 knockdown led to a suppression of the expression of mesodermal and mesoendodermal but not ectodermal markers. The differentiation suppressions were further confirmed by the impaired differentiation of mesodermal and some of the endodermal but not ectodermal derivatives. Such defects were partially because of the increased apoptosis in Flk-1+ cells. These findings provide the first demonstration of the important role of IP3R3 in the regulation of apoptosis in early differentiating ES cells and subsequent lineage commitments through modulation of Ca2+ signals.
