Context-Dependent Wiring of Sox2 Regulatory Networks for Self-Renewal of Embryonic and Trophoblast Stem Cells
Context-Dependent Wiring of Sox2 Regulatory Networks for Self-Renewal of Embryonic and Trophoblast Stem Cells
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DOI：
10.1016/j.molcel.2013.09.002
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发表时间：
2013-11-07
期刊：
影响因子：
16
通讯作者：
Niwa, Hitoshi
中科院分区：
文献类型：
--
作者：
Adachi, Kenjiro;Nikaido, Itoshi;Niwa, Hitoshi
Sox 2是维持多能性所需的转录因子。它也在不同类型的多能干细胞中发挥重要作用，提高了Sox 2控制常见干细胞表型的可能性。在这里，我们表明，Sox 2是成纤维细胞生长因子（FGF）信号传导的关键下游靶点，其介导滋养层干细胞（TSCs）的自我更新。Sox2与Esrrb或Tfap2c的持续表达可以替代FGF依赖性。通过比较胚胎干细胞（ESC）和TSCs中Sox 2的全基因组结合位点与诱导型敲除系统的结合，我们发现，尽管Sox 2在保护干细胞状态方面具有共同的作用，但Sox 2在这两种不同但发育相关的干细胞类型中调节具有独特功能的不同基因组。我们的研究结果提供了深入了解胚胎发生过程中转录因子的功能多样性，在此期间，它们可以递归地利用离散的网络结构内的可变方式。
Sox2 is a transcription factor required for the maintenance of pluripotency. It also plays an essential role in different types of multipotent stem cells, raising the possibility that Sox2 governs the common sternness phenotype. Here we show that Sox2 is a critical downstream target of fibroblast growth factor (FGF) signaling, which mediates self-renewal of trophoblast stem cells (TSCs). Sustained expression of Sox2 together with Esrrb or Tfap2c can replace FGF dependency. By comparing genome-wide binding sites of Sox2 in embryonic stem cells (ESCs) and TSCs combined with inducible knockout systems, we found that, despite the common role in safeguarding the stem cell state, Sox2 regulates distinct sets of genes with unique functions in these two different yet developmentally related types of stem cells. Our findings provide insights into the functional versatility of transcription factors during embryogenesis, during which they can be recursively utilized in a variable manner within discrete network structures.