Oct-4 controls cell-cycle progression of embryonic stem cells.
Oct-4 controls cell-cycle progression of embryonic stem cells.
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DOI：
10.1042/bj20091439
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发表时间：
2010-02-09
期刊：
影响因子：
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通讯作者：
Kim J
中科院分区：
文献类型：
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作者：
Lee J;Go Y;Kang I;Han YM;Kim J
小鼠和人类胚胎干细胞表现出不同寻常的增殖特性，可以无限地产生多能干细胞。这两个过程对于维持胚胎干细胞的“干性”可能都很重要；然而，对于胚胎干细胞的细胞周期命运是如何调控的，我们知之甚少。Oct-4是多能性的主开关，在维持胚胎干细胞的多能性状态中起重要作用，并可能阻止分化过程中激活的基因的表达。我们利用ZHBTc4 ES细胞研究了Oct-4对ES细胞周期调控的影响，发现Oct-4下调在ES细胞G0/G1期通过阻断细胞周期进程抑制细胞增殖。Oct-4功能域的缺失分析表明，Oct-4功能域的整体完整性对于刺激s期进入很重要。我们在目前的研究中也表明p21基因是Oct-4抑制的靶标。此外，在ZHBTc4 ES细胞中，Oct-4抑制p21蛋白水平，并通过下调Oct-4诱导p21蛋白水平。因此，Oct-4下调p21可能有助于维持胚胎干细胞的增殖。
Mouse and human ES (embryonic stem) cells display unusual proliferative properties and can produce pluripotent stem cells indefinitely. Both processes might be important for maintaining the ‘stemness’ of ES cells; however, little is known about how the cell-cycle fate is regulated in ES cells. Oct-4, a master switch of pluripotency, plays an important role in maintaining the pluripotent state of ES cells and may prevent the expression of genes activated during differentiation. Using ZHBTc4 ES cells, we have investigated the effect of Oct-4 on ES cell-cycle control, and we found that Oct-4 down-regulation in ES cells inhibits proliferation by blocking cell-cycle progression in G0/G1. Deletion analysis of the functional domains of Oct-4 indicates that the overall integrity of the Oct-4 functional domains is important for the stimulation of S-phase entry. We also show in the present study that the p21 gene is a target for Oct-4 repression. Furthermore, p21 protein levels were repressed by Oct-4 and were induced by the down-regulation of Oct-4 in ZHBTc4 ES cells. Therefore the down-regulation of p21 by Oct-4 may contribute to the maintenance of ES cell proliferation.