胚胎干細(xì)胞（embryonic stem cells, ESCs）自我更新和分化命運(yùn)的決定受胞內(nèi)外信號分子共同精細(xì)地調(diào)控,。鈣信號對細(xì)胞的多種生理活動,，例如細(xì)胞的增殖、凋亡和分化都具有重要的調(diào)控作用,。內(nèi)質(zhì)網(wǎng)三磷酸肌醇.受體（IP3R）是胞內(nèi)重要的鈣離子釋放受體,，在ESCs中存在著三種IP3R亞型，但它們在胚胎干細(xì)胞中的作用并不清楚,。
1月15日,， Cell Death and Differentiation雜志在線發(fā)表了中國科學(xué)院上海生命科學(xué)研究院/上海交通大學(xué)醫(yī)學(xué)院健康科學(xué)研究所楊黃恬研究組的最新研究工作“Type 3 inositol 1,4,5-trisphosphate receptor negatively regulates apoptosis during mouse embryonic stem cell differentiation”。以往人們一般認(rèn)為IP3R3介導(dǎo)的鈣信號是一種促凋亡因子,。博士研究生梁冀和其他研究組成員在楊黃恬研究員的指導(dǎo)下證明在胚胎干細(xì)胞早期分化過程中IP3R3介導(dǎo)的鈣信號發(fā)揮著抗凋亡作用,，IP3R3通過控制早期胚層細(xì)胞的凋亡在胚胎干細(xì)胞的中胚層和部分內(nèi)胚層分化命運(yùn)的決定中發(fā)揮著重要的調(diào)控作用,。這一研究發(fā)現(xiàn)豐富了對IP3R調(diào)控的鈣信號參與胚胎干細(xì)胞分化命運(yùn)決定的認(rèn)識，揭示了胚胎干細(xì)胞分化過程中的凋亡活動與胚層分化命運(yùn)決定之間的關(guān)聯(lián)和其調(diào)控新機(jī)制,。（生物谷Bioon.com）
楊黃恬老師4月份將出席“干細(xì)胞技術(shù)與應(yīng)用講座”,，詳情見：http://www.stemcellasia.net/
生物谷推薦原始出處：
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.
