Mouse embryonic stem cells (mESCs) exist in two distinct pluripotent states: the naive and the primed. Mainly by inducing differentiation of mESCs in vitro, conducting RNA sequencing analyses, and specifying expression of the regulatory genes, we explored the regulatory mechanisms underlying the transition between the naive and primed states. We found that, under the defined differentiation-inducing conditions, the naive state of mESCs shifted to the primed state within two days of differentiation induction, during which the cell cycle- and differentiation-related proteins changes significantly. Specifically, we uncovered that the expression of STAG2, a subunit of the Cohesin complex, was upregulated. We further revealed that knockout of STAG2 resulted in upregulation of the naive gene sets and downregulation of the primed gene sets, indicating importance of STAG2 in regulating the naive-primed transition. More importantly, STAG2 knockout led to a reduction in number of the bivalent genes, a decrease in Lin28a transcription, and a reduced cytoplasmic localization of Lin28a. Overexpressing Lin28a or a Lin28a variant lacking the nucleolar localization signal (Lin28aΔNoLS) in STAG2 knockout cells rescued the downregulation of the primed marker genes Dnmt3a/3b. Collectively, we conclude that STAG2 facilitates the naive-primed transition of mESCs by activating Lin28a transcription and that this work may offer a new insight into the regulation of pluripotency in mESCs.

中文翻译：

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STAG2 通过激活小鼠胚胎干细胞中的 Lin28a 转录来促进幼稚引发的转化。


小鼠胚胎干细胞 （mESC） 以两种不同的多能状态存在：幼稚和初发。主要通过在体外诱导 mESCs 分化、进行 RNA 测序分析和指定调节基因的表达，我们探索了幼稚状态和启动状态之间转变的潜在调节机制。我们发现，在确定的分化诱导条件下，mESCs 的幼稚状态在分化诱导后 2 天内转变为引发状态，在此期间细胞周期和分化相关蛋白发生显着变化。具体来说，我们发现 Cohesin 复合体的一个亚基 STAG2 的表达上调。我们进一步揭示，STAG2 的敲除导致幼稚基因集的上调和引发基因集的下调，表明 STAG2 在调节幼稚引发转换中的重要性。更重要的是，STAG2 敲除导致二价基因数量减少，Lin28a 转录减少，Lin28a 细胞质定位减少。在 STAG2 敲除细胞中过表达 Lin28a 或缺乏核仁定位信号 （Lin28aΔNoLS） 的 Lin28a 变体挽救了引发标记基因 Dnmt3a/3b 的下调。总的来说，我们得出结论，STAG2 通过激活 Lin28a 转录促进 mESC 的幼稚引发转变，这项工作可能为 mESC 中多能性的调节提供新的见解。