Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
Stem Cells Dev. 2012 Mar 20;21(5):710-20. doi: 10.1089/scd.2011.0085. Epub 2011 Jul 8.
Embryonic stem cells (ESCs) maintain their pluripotency through high expression of pluripotency-related genes. Here, we show that differing levels of Oct4, Nanog, and c-myc proteins among the individual cells of mouse ESC (mESC) colonies and fluctuations in these levels do not disturb mESC pluripotency. Cells with strong expression of Oct4 had low levels of Nanog and c-myc proteins and vice versa. In addition, cells with high levels of Nanog tended to occupy interior regions of mESC colonies. In contrast, peripherally positioned cells within colonies had dense H3K27-trimethylation, especially at the nuclear periphery. We also observed distinct levels of endogenous and exogenous Oct4 in particular cell cycle phases. The highest levels of Oct4 occurred in G2 phase, which correlated with the pKi-67 nuclear pattern. Moreover, the Oct4 protein resided on mitotic chromosomes. We suggest that there must be an endogenous mechanism that prevents the induction of spontaneous differentiation, despite fluctuations in protein levels within an mESC colony. Based on the results presented here, it is likely that cells within a colony support each other in the maintenance of pluripotency.
胚胎干细胞（ESCs）通过高水平表达多能性相关基因来维持其多能性。在这里，我们表明，在小鼠 ESC（mESC）集落的单个细胞之间，Oct4、Nanog 和 c-myc 蛋白的水平存在差异，并且这些水平的波动不会干扰 mESC 的多能性。具有强 Oct4 表达的细胞具有低水平的 Nanog 和 c-myc 蛋白，反之亦然。此外，高表达 Nanog 的细胞往往占据 mESC 集落的内部区域。相比之下，集落中位于外围的细胞具有密集的 H3K27-三甲基化，特别是在核周。我们还观察到特定细胞周期相中有明显不同水平的内源性和外源性 Oct4。Oct4 水平最高出现在 G2 期，与 pKi-67 核模式相关。此外，Oct4 蛋白位于有丝分裂染色体上。我们认为，尽管 mESC 集落中的蛋白水平波动，但一定存在一种内源性机制来防止自发分化的诱导。基于这里呈现的结果，集落中的细胞很可能相互支持以维持多能性。
