Apoptosis and differentiation commitment:: novel insights revealed by gene profiling studies in mouse embryonic stem cells
Apoptosis and differentiation commitment:: novel insights revealed by gene profiling studies in mouse embryonic stem cells
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DOI：
10.1038/sj.cdd.4401789
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发表时间：
2006-04-01
影响因子：
12.4
通讯作者：
Bouf, H
中科院分区：
文献类型：
--
作者：
Duval, D;Trouillas, M;Bouf, H
小鼠胚胎干 (ES) 细胞在白血病抑制因子 (LIF) 存在下生长时，在体外仍保持多能性。 LIF 饥饿导致一些 ES 衍生的分化细胞凋亡，同时激活 p38 α 丝裂原激活蛋白激酶 (MAPK)。 p38 抑制剂 PD169316 可阻断细胞凋亡，但不会阻断细胞形态分化。为了进一步了解该化合物的作用机制，我们通过微阵列研究确定了其特定靶点。我们报告了与多能细胞相比，LIF 撤除后 3 天（d3）表达的基因的整体表达谱，以及在抗凋亡条件下在 d3 表达受调节的基因的总体表达谱。我们发现，在第 3 天，没有 LIF 的细胞比预期更早地表达特化细胞标记物，并且当细胞凋亡过程受损时，分化标记物的表达会发生改变。此外，功能测试揭示了抗凋亡蛋白不会改变细胞多能性的特性，以及金属硫蛋白 1 基因的新作用，可防止早期分化细胞的凋亡。
Mouse embryonic stem (ES) cells remain pluripotent in vitro when grown in the presence of leukemia inhibitory factor (LIF). LIF starvation leads to apoptosis of some of the ES-derived differentiated cells, together with p38 alpha mitogen-activated protein kinase ( MAPK) activation. Apoptosis, but not morphological cell differentiation, is blocked by a p38 inhibitor, PD169316. To further understand the mechanism of action of this compound, we have identified its specific targets by microarray studies. We report on the global expression profiles of genes expressed at 3 days upon LIF withdrawal (d3) compared to pluripotent cells and of genes whose expression is modulated at d3 under anti-apoptotic conditions. We showed that at d3 without LIF cells express, earlier than anticipated, specialized cell markers and that when the apoptotic process was impaired, expression of differentiation markers was altered. In addition, functional tests revealed properties of anti-apoptotic proteins not to alter cell pluripotency and a novel role for metallothionein 1 gene, which prevents apoptosis of early differentiated cells.