Sox2 expression effects on direct reprogramming efficiency as determined by alternative somatic cell fate.
Sox2 expression effects on direct reprogramming efficiency as determined by alternative somatic cell fate.
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DOI：
10.1016/j.scr.2010.09.004
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发表时间：
2011-03
影响因子：
1.2
通讯作者：
S. Yamaguchi;Kunio Hirano;Shogo Nagata;T. Tada
中科院分区：
文献类型：
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作者：
S. Yamaguchi;Kunio Hirano;Shogo Nagata;T. Tada
诱导多能干细胞 (iPSC) 是通过直接重编程体细胞而产生的，方法是迫使体细胞表达外源转录因子 Oct4、Sox2、Klf4 和 c-Myc (OSKM)。这些细胞有可能用于临床应用和基础研究。在这里，我们通过生成不同水平表达 Sox2 的 iPSC 来探索 Sox2 的分子作用。低 Sox2 (LS) 表达与 OKM 结合提高了生成部分重编程 iPSC 的效率。值得注意的是，我们检测到具有 OK 和 LS 三个因素的完全重编程 iPSC 的数量显着增加。 LS 表达与外胚层和中胚层标记基因表达的减少有关。这表明细胞分化为外胚层和中胚层谱系在重编程过程中受到阻碍。从多能标记基因表达和嵌合体形成来看，使用 OK 和 LS 生成的 iPSC 的质量与通过传统 OSK 生成的 iPSC 的质量相当。我们得出结论，Sox2 在体细胞直接重编程为 iPSC 的过程中以剂量依赖性方式发挥着至关重要的作用。
Induced pluripotent stem cells (iPSCs) are generated by directly reprogramming somatic cells by forcing them to express the exogenous transcription factors, Oct4, Sox2, Klf4 and c-Myc (OSKM). These cells could potentially be used in clinical applications and basic research. Here, we explored the molecular role of Sox2 by generating iPSCs that expressed Sox2 at various levels. Low Sox2 (LS) expression increased the efficiency of generating partially reprogrammed iPSCs in combination with OKM. Notably, we detected a significant increase in the number of fully reprogrammed iPSCs with three factors of OK and LS. LS expression was linked with the reduced expression of ectoderm and mesoderm marker genes. This indicates that cell differentiation into the ectoderm and mesoderm lineages was impeded during reprogramming. The quality of the iPSCs that was generated by using OK and LS was comparable to that of iPSCs that were produced via conventional OSK as seen by pluripotent marker gene expression and chimera formation. We conclude that Sox2 plays a crucial role in a dose-dependent manner in direct reprogramming of somatic cells to iPSCs.