Type 3 inositol 1,4,5-trisphosphate receptor negatively regulates apoptosis during mouse embryonic stem cell differentiation
Type 3 inositol 1,4,5-trisphosphate receptor negatively regulates apoptosis during mouse embryonic stem cell differentiation
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3型肌醇1,4,5-三磷酸受体负向调节小鼠胚胎干细胞分化过程中的细胞凋亡
DOI：
10.1038/cdd.2009.209
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发表时间：
2010-01
影响因子：
12.4
通讯作者：
Wang, Y-J
中科院分区：
文献类型：
--
作者：
Liang, J.;Cao, N.;Tang, Y.;Wang, J.;Yang, H-T;Wang, Y-J
三磷酸肌醇受体（IP（3）Rs）产生的Ca（2+）信号对细胞凋亡和分化等细胞过程至关重要。然而，IP（3）Rs的确切作用及其对多能胚胎干细胞（ES细胞）行为中Ca（2+）信号的贡献在很大程度上仍然未知。在这项研究中，我们发现，3型IP（3）R（IP（3）R3）的表达是短暂下调，伴随着在小鼠ES细胞的早期分化阶段的凋亡增加。小干扰RNA敲低IP（3）R3可增加分化中细胞的凋亡，但不影响未分化的ES细胞。此外，IP（3）R3过表达具有相反的作用。一致地，IP（3）R3敲除改变了分化细胞中的Ca（2+）振荡，但没有改变未分化ES细胞中的Ca（2+）振荡。用BAPTA-AM螯合胞内Ca（2+）可减少IP（3）R3敲低分化细胞的凋亡，而增加对照细胞的凋亡。此外，IP（3）R3敲低导致中胚层和中内胚层标记物的表达抑制，但不抑制外胚层标记物的表达。中胚层和部分内胚层衍生物分化受损而外胚层未分化，进一步证实了分化障碍。这种缺陷部分是由于Flk-1（+）细胞凋亡增加所致。这些发现首次证明了IP（3）R3通过调节Ca（2+）信号在早期分化的ES细胞中调节凋亡和随后的谱系定型中的重要作用。
Ca(2+) signals generated by inositol 1,4,5-trisphosphate receptors (IP(3)Rs) are crucial for cellular processes such as apoptosis and differentiation. However, the exact roles of IP(3)Rs and their contributions to Ca(2+) signals in pluripotent embryonic stem (ES) cell behaviors remain largely unknown. In this study, we showed that the expression of type 3 IP(3)R (IP(3)R3) was transiently downregulated with a concomitant increase in apoptosis at the early differentiation stage of murine ES cells. Knockdown of IP(3)R3 by small interfering RNA increased apoptosis in differentiating cells but not in undifferentiated ES cells. Moreover, IP(3)R3 overexpression had the opposite effect. Consistently, IP(3)R3 knockdown altered Ca(2+) oscillations in differentiating cells but not in undifferentiated ES cells. The apoptosis in differentiating IP(3)R3-knockdown cells was decreased by chelating intracellular Ca(2+) with BAPTA-AM and increased in control ones. Furthermore, IP(3)R3 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 IP(3)R3 in the regulation of apoptosis in early differentiating ES cells and subsequent lineage commitments through modulation of Ca(2+) signals.
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DOI：
--
发表时间：
1999
期刊：
--
影响因子：
--
作者：
Guylain Boulay;Darren M. Brown;Ning Qin;Meisheng Jiang;Alexander Dietrich;Michael Xi Zhu;Zhangguo Chen;M. Birnbaumer;Katsuhiko Mikoshiba;Lutz Birnbaumer
通讯作者：
Guylain Boulay;Darren M. Brown;Ning Qin;Meisheng Jiang;Alexander Dietrich;Michael Xi Zhu;Zhangguo Chen;M. Birnbaumer;Katsuhiko Mikoshiba;Lutz Birnbaumer
从稳定转染的 COS-1 细胞中生产和纯化重组水牛白血病抑制因子 (rBuLIF)
DOI：
10.1096/fj.99-0810com
发表时间：
2015
期刊：
The FASEB Journal
影响因子：
--
作者：
G. Kaur;N. Das;S. Kumar
通讯作者：
S. Kumar
影响因子：
4.8
作者：
Ashworth, Rachel;Devogelaere, Benoit;Patel, Sandip
通讯作者：
Patel, Sandip
DOI：
10.1016/j.bbrc.2006.07.020
发表时间：
2006-09-08
影响因子：
3.1
作者：
Wang, Bei Bei;Lu, Rui;Jin, Ying
通讯作者：
Jin, Ying
影响因子：
4.6
作者：
J. Stachecki;D. Armant
通讯作者：
J. Stachecki;D. Armant