MicroRNAs control the apoptotic threshold in primed pluripotent stem cells through regulation of BIM.
MicroRNAs control the apoptotic threshold in primed pluripotent stem cells through regulation of BIM.
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DOI：
10.1101/gad.245621.114
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发表时间：
2014-09-01
影响因子：
10.5
通讯作者：
Rodríguez TA
中科院分区：
文献类型：
--
作者：
Pernaute B;Spruce T;Smith KM;Sánchez-Nieto JM;Manzanares M;Cobb B;Rodríguez TA
Pernaute等人将miRNA介导的调节确定为控制植入后上胚层细胞凋亡的关键机制。三个miRNA家族，miR-20，miR-92和miR-302，通过微调促凋亡蛋白BIM的表达水平来控制线粒体凋亡机制。需要这些miRNA家族来维持干细胞中的细胞存活，所述干细胞不仅分化而且细胞死亡。哺乳动物致敏多能干细胞由于其低凋亡阈值而对细胞死亡刺激高度敏感，但该阈值如何调节仍在很大程度上未知。在这里，我们确定microRNA（miRNA）介导的调节作为一个关键机制控制植入后上胚层细胞凋亡。此外，我们发现三个miRNA家族，miR-20，miR-92和miR-302，通过微调促凋亡蛋白BIM的表达水平来控制线粒体凋亡机制。因此，这些家族代表了维持干细胞中细胞存活所需的基本缓冲液，所述干细胞不仅分化而且细胞死亡。
Pernaute et al. identify miRNA-mediated regulation as a key mechanism controlling apoptosis in the post-implantation epiblast. Three miRNA families, miR-20, miR-92, and miR-302, control the mitochondrial apoptotic machinery by fine-tuning the levels of expression of the proapoptotic protein BIM. These miRNA families are needed to maintain cell survival in stem cells that are primed for not only differentiation but also cell death. Mammalian primed pluripotent stem cells have been shown to be highly susceptible to cell death stimuli due to their low apoptotic threshold, but how this threshold is regulated remains largely unknown. Here we identify microRNA (miRNA)-mediated regulation as a key mechanism controlling apoptosis in the post-implantation epiblast. Moreover, we found that three miRNA families, miR-20, miR-92, and miR-302, control the mitochondrial apoptotic machinery by fine-tuning the levels of expression of the proapoptotic protein BIM. These families therefore represent an essential buffer needed to maintain cell survival in stem cells that are primed for not only differentiation but also cell death.