Fong Helen, Hohenstein Kristi A, Donovan Peter J
Sue and Bill Gross Stem Cell Research Program, Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California, USA.
Stem Cells. 2008 Aug;26(8):1931-8. doi: 10.1634/stemcells.2007-1002. Epub 2008 Apr 3.
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. Disclosure of potential conflicts of interest is found at the end of this article.
源自囊胚的人类胚胎干细胞（hES细胞）能够无限自我更新并分化为身体的所有细胞谱系。由于其多能性本质，hES细胞是理解人类发育和推动再生医学领域发展的宝贵工具。然而，将hES细胞的治疗潜力应用于生物医学的一个关键始于确定这些细胞如何维持其多能和未分化状态。对小鼠的研究表明，有三种因子参与调节胚胎干细胞的多能性，即Oct4、Nanog和Sox2。然而，已发现小鼠胚胎干细胞和hES细胞在生长调节方面存在显著差异，这表明需要确定这些因子在hES细胞中何时以及如何发挥作用。迄今为止，通过对hES细胞的功能研究，转录因子Oct4和Nanog已被确定为干细胞命运的关键调节因子。为了确定Sox2在维持hES细胞多能性和自我更新中的作用，我们使用RNA干扰特异性敲低Sox2基因表达。hES细胞中Sox2表达的降低导致未分化干细胞状态的丧失，这表现为细胞形态的改变、干细胞标志物表达的改变以及滋养外胚层标志物表达的增加。此外，Sox2的敲低导致包括Oct4和Nanog在内的几种关键干细胞因子的表达降低，将这三种因子在一个多能调节网络中联系在一起。潜在利益冲突的披露见本文末尾。
