Role of SOX2 in maintaining pluripotency of human embryonic stem cells
Role of SOX2 in maintaining pluripotency of human embryonic stem cells
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DOI：
10.1111/j.1365-2443.2010.01400.x
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发表时间：
2010-05-01
期刊：
影响因子：
2.1
通讯作者：
Kawase, Eihachiro
中科院分区：
文献类型：
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作者：
Adachi, Keiko;Suemori, Hirofumi;Kawase, Eihachiro
人类胚胎干细胞（ESC）的多能性被认为是由几个关键的转录因子，包括OCT 4，NANOG和SOX 2调节。虽然OCT 4和NANOG在人类ESC中的功能已经明确，但SOX 2的功能尚未完全表征。为了研究SOX 2的作用，我们调节了人ESC中SOX 2的表达水平。人胚胎干细胞中SOX 2表达的减少诱导了滋养外胚层和部分内胚层分化。有趣的是，CDX 2，一个典型的滋养外胚层相关基因，没有上调。相比之下，使用Tet-on基因诱导系统，人ESC中SOX 2的过表达诱导滋养外胚层分化，伴随着CDX 2表达的增加。此外，S 0X 2过表达导致CG α阳性细胞的增加，这标志着后期滋养外胚层发育，而不是胎盘催乳素阳性细胞。因此，人ESC中SOX 2表达的过表达以及抑制导致其分化为滋养外胚层谱系。我们的数据表明，SOX 2在维持人类胚胎干细胞的多能性和可能的滋养层发育中起着重要作用。
Human embryonic stem cell (ESC) pluripotency is thought to be regulated by several key transcription factors including OCT4, NANOG, and SOX2. Although the functions of OCT4 and NANOG in human ESCs are well defined, that of SOX2 has not been fully characterized. To investigate the role of SOX2, we modulated the level of SOX2 expression in human ESCs. Reduction of SOX2 expression in human ESCs induced trophectodermal and partial endodermal differentiation. Interestingly, CDX2, a typical trophectoderm-associated gene, was not up-regulated. In contrast, using the Tet-on gene inducible system, SOX2 over-expression in human ESCs induced trophectoderm differentiation accompanied by increased CDX2 expression. Additionally, SOX2 over-expression resulted in an increase in CG alpha-positive cells, which marks later stage trophectoderm development, rather than placental lactogen-positive cells. Thus, over-expression as well as repression of SOX2 expression in human ESCs resulted in their differentiation into the trophectoderm lineage. Our data show that SOX2 plays an important role in the maintenance of pluripotency of human ESCs and possibly, trophoblast development.