Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 6500047, Japan.
Mol Cell. 2013 Nov 7;52(3):380-92. doi: 10.1016/j.molcel.2013.09.002. Epub 2013 Oct 10.
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 stemness 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.
Sox2 是一种转录因子，对于维持多能性是必需的。它在不同类型的多能干细胞中也起着至关重要的作用，这使得 Sox2 有可能控制共同的干性表型。在这里，我们表明 Sox2 是成纤维细胞生长因子 (FGF) 信号转导的关键下游靶标，该信号转导介导滋养层干细胞 (TSC) 的自我更新。持续表达 Sox2 与 Esrrb 或 Tfap2c 一起可以替代 FGF 的依赖性。通过比较 Sox2 在胚胎干细胞 (ESCs) 和 TSCs 中的全基因组结合位点，结合诱导型敲除系统，我们发现，尽管 Sox2 在维持干细胞状态方面具有共同作用，但 Sox2 在这两种不同但发育相关的干细胞中调节着具有独特功能的不同基因集。我们的研究结果为转录因子在胚胎发生过程中的功能多样性提供了新的认识，在此过程中，它们可以在离散的网络结构内以可变的方式递归地利用。
