Regulation of self-renewal and pluripotency by Sox2 in human embryonic stem cells
Regulation of self-renewal and pluripotency by Sox2 in human embryonic stem cells
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DOI：
10.1634/stemcells.2007-1002
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发表时间：
2008-08-01
期刊：
影响因子：
5.2
通讯作者：
Donovan, Peter J.
中科院分区：
文献类型：
--
作者：
Fong, Helen;Hohenstein, Kristi A.;Donovan, Peter J.
人胚胎干细胞（human embryonic stem cells，hES）是一种具有无限自我更新能力和分化能力的细胞，可分化为多种细胞系。由于其多能性，hES细胞是了解人类发育和推进再生医学领域的宝贵工具。然而，利用hES细胞的治疗能力用于生物医学应用的一个关键是确定这些细胞如何保持其多能性和未分化状态。在小鼠中的研究表明，有三种因子调节胚胎干细胞的多能性：Oct4、Nanog和Sox 2。然而，小鼠胚胎干细胞和hES细胞之间的生长调节的显着差异已被确定，这表明需要确定何时以及如何因素在hES细胞中工作。迄今为止，转录因子Oct4和Nanog已被鉴定为通过在hES细胞中的功能研究的干细胞命运的关键调节剂。为了确定Sox 2在维持hES细胞多能性和自我更新中的作用，我们使用RNA干扰来特异性敲低Sox 2基因表达。hES细胞中Sox 2表达的减少导致未分化干细胞状态的丧失，如细胞形态学的变化、干细胞标志物表达的改变和滋养外胚层标志物表达的增加所示。此外，Sox 2的敲低导致几种关键干细胞因子的表达减少，包括Oct4和Nanog，将这三种因子连接在多能调控网络中。
Human embryonic stem (hES) cells, derived from blastocysts, are capable of unlimited self-renewal and differentiation into all cell lineages of the body. Because of their pluripotent nature, hES cells are valuable tools for understanding human development and advancing the field of regenerative medicine. However, one key to harnessing the therapeutic power of hES cells for biomedical applications begins with determining how these cells maintain their pluripotent and undifferentiated state. Studies in mice have implicated three factors in regulating pluripotency in embryonic stem cells, Oct4, Nanog, and Sox2. However, significant differences in growth regulation between mouse embryonic stem and hES cells have been identified, suggesting a need to determine when and how factors work in hES cells. To date, the transcription factors Oct4 and Nanog have been identified as critical regulators of stem cell fate by functional studies in hES cells. To determine the role of Sox2 in maintaining hES cell pluripotency and self-renewal, we used RNA interference to specifically knock down Sox2 gene expression. Reduction of Sox2 expression in hES cells results in loss of the undifferentiated stem cell state, as indicated by a change in cell morphology, altered stem cell marker expression, and increased expression of trophectoderm markers. In addition, knockdown of Sox2 results in reduced expression of several key stem cell factors, including Oct4 and Nanog, linking these three factors together in a pluripotent regulatory network.