Chamberlain Stormy J, Yee Della, Magnuson Terry
Department of Genetics and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Stem Cells. 2008 Jun;26(6):1496-505. doi: 10.1634/stemcells.2008-0102. Epub 2008 Apr 10.
Polycomb repressive complex 2 (PRC2) methylates histone H3 tails at lysine 27 and is essential for embryonic development. The three core components of PRC2, Eed, Ezh2, and Suz12, are also highly expressed in embryonic stem (ES) cells, where they are postulated to repress developmental regulators and thereby prevent differentiation to maintain the pluripotent state. We performed gene expression and chimera analyses on low- and high-passage Eed(null) ES cells to determine whether PRC2 is required for the maintenance of pluripotency. We report here that although developmental regulators are overexpressed in Eed(null) ES cells, both low- and high-passage cells are functionally pluripotent. We hypothesize that they are pluripotent because they maintain expression of critical pluripotency factors. Given that EED is required for stability of EZH2, the catalytic subunit of the complex, these data suggest that PRC2 is not necessary for the maintenance of the pluripotent state in ES cells. We propose a positive-only model of embryonic stem cell maintenance, where positive regulation of pluripotency factors is sufficient to mediate stem cell pluripotency. Disclosure of potential conflicts of interest is found at the end of this article.
多梳抑制复合物2（PRC2）使组蛋白H3尾部的赖氨酸27发生甲基化，对胚胎发育至关重要。PRC2的三个核心组分Eed、Ezh2和Suz12在胚胎干细胞（ES细胞）中也高度表达，据推测它们在ES细胞中抑制发育调节因子，从而防止分化以维持多能状态。我们对低传代和高传代的Eed基因敲除ES细胞进行了基因表达和嵌合体分析，以确定PRC2对于维持多能性是否必需。我们在此报告，尽管发育调节因子在Eed基因敲除ES细胞中过度表达，但低传代和高传代细胞在功能上均具有多能性。我们推测它们具有多能性是因为它们维持关键多能性因子的表达。鉴于EED对于复合物的催化亚基EZH2的稳定性是必需的，这些数据表明PRC2对于维持ES细胞的多能状态并非必要。我们提出了一种仅正向调节的胚胎干细胞维持模型，即多能性因子的正向调节足以介导干细胞的多能性。潜在利益冲突的披露见本文末尾。
