Caspase activity mediates the differentiation of embryonic stem cells
Caspase activity mediates the differentiation of embryonic stem cells
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DOI：
10.1016/j.stem.2008.04.001
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发表时间：
2008-06-01
期刊：
影响因子：
23.9
通讯作者：
Zwaka, Thomas P.
中科院分区：
文献类型：
--
作者：
Fujita, Jun;Crane, Ana M.;Zwaka, Thomas P.
胚胎干细胞（ESC）能够无限自我更新，同时保留分化为三个胚层中任何一个的能力，这些胚层产生所有体细胞类型。一个新兴的观点是，一组核心转录因子，包括Oct4，Sox 2和Nanog，形成了一个强大的自动调节电路，使ESC保持在自我更新状态。为了适应这些细胞进行胚层特异性分化的能力，我们预测了一种翻译后机制，可以负调控这些核心自我更新因子。在这里，我们报告了半胱天冬酶诱导的Nanog切割在分化的胚胎干细胞中的作用。缺乏Casp3基因的干细胞表现出明显的分化缺陷，而在ESCs中强制表达抗半胱天冬酶切割的Nanog突变体强烈促进了自我更新。这些结果将程序性细胞死亡途径的主要组成部分与ESC发育的调节联系起来。
Embryonic stem cells (ESCs) are capable of indefinite self-renewal while retaining the ability to differentiate to any of the three germ layers that give rise to all somatic cell types. An emerging view is that a core set of transcription factors, including Oct4, Sox2, and Nanog, form a robust autoregulatory circuit that maintains ESCs in a self-renewing state. To accommodate the capacity of such cells to undergo germ layer-specific differentiation, we predicted a posttranslational mechanism that could negatively regulate these core self-renewal factors. Here we report caspase-induced cleavage of Nanog in differentiating ESCs. Stem cells lacking the Casp3 gene showed marked defects in differentiation, while forced expression of a caspase cleavage-resistant Nanog mutant in ESCs strongly promoted self-renewal. These results link a major component of the programmed cell-death pathway to the regulation of ESC development.