Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells
Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells
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DOI：
10.1038/ncb1589
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发表时间：
2007-06-01
影响因子：
21.3
通讯作者：
Niwa, Hitoshi
中科院分区：
文献类型：
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作者：
Masui, Shinji;Nakatake, Yuhki;Niwa, Hitoshi
胚胎干细胞（ES）的多能性被认为是由一些关键的转录因子维持的，包括Oct 3/4和Sox 2。Oct 3/4在ES细胞中的功能已被广泛表征，但Sox 2的功能尚未确定。Sox 2可以在体外与Oct 3/4协同作用以激活Oct-Sox增强子，其调节多能干细胞特异性基因的表达，包括Nanog，Oct 3/4和Sox 2本身。这些发现表明，Sox 2是ES细胞所需的Oct-Sox增强剂活性。使用可诱导的Sox 2-null小鼠ES细胞，我们表明，Sox 2的激活这些Oct-Sox增强子。相反，我们证明，Sox 2是必要的调节多种转录因子，影响Oct 3/4的表达和Oct 3/4的强制表达拯救Sox 2空ES细胞的多能性。这些结果表明，Sox 2的基本功能是通过维持Oct 3/4表达的必要水平来稳定ES细胞处于多能状态。
The pluripotency of embryonic stem (ES) cells is thought to be maintained by a few key transcription factors, including Oct3/4 and Sox2. The function of Oct3/4 in ES cells has been extensively characterized, but that of Sox2 has yet to be determined. Sox2 can act synergistically with Oct3/4 in vitro to activate Oct-Sox enhancers, which regulate the expression of pluripotent stem cell-specific genes, including Nanog, Oct3/4 and Sox2 itself. These findings suggest that Sox2 is required by ES cells for its Oct-Sox enhancer activity. Using inducible Sox2-null mouse ES cells, we show that Sox2 is dispensable for the activation of these Oct-Sox enhancers. In contrast, we demonstrate that Sox2 is necessary for regulating multiple transcription factors that affect Oct3/4 expression and that the forced expression of Oct3/4 rescues the pluripotency of Sox2-null ES cells. These results indicate that the essential function of Sox2 is to stabilize ES cells in a pluripotent state by maintaining the requisite level of Oct3/4 expression.