Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kinki University Faculty of Medicine, Osaka, Japan.
Stem Cells Dev. 2012 May 20;21(8):1239-49. doi: 10.1089/scd.2011.0322. Epub 2011 Oct 18.
Recently, an additional type of pluripotent stem cell-line derived from mouse embryos has been established and termed epiblast stem cell (EpiSC), and is expected to be an important tool for studying the mechanisms of maintenance of pluripotency since they depend on basic fibroblast growth factor-MAPK and Activin A-Smad2/3 signaling to maintain pluripotency, unlike mouse embryonic stem cells (ESCs). Further, because of the similarities between mouse EpiSCs and human ESCs, EpiSCs are expected to be effective experimental models for human stem cell therapy. Recently, study for conversion from ESC state to EpiSC state or reversion from EpiSC state to ESC state has attracted interest since these techniques may lead to increasing the potential of pluripotent stem cells and our knowledge about their developmental status. In the present study, we find that a low oxygen concentration in culture environment accelerated, improved, and stabilized the EpiSC state of the converted cells from the ESC state using Oct4ΔPE-GFP transgenic ESCs. Induced EpiSCs (iEpiSCs) in hypoxia possess closer gene expression patterns to native EpiSCs, and bisulfite sequences for the promoter regions of Stella and Oct4 genes have elucidated that the iEpiSC gain EpiSC-specific methylation patterns in hypoxia. Our data provide evidence that oxygen concentration is an important factor for establishment of the EpiSC-specific state.
最近，已经建立了另一种源自小鼠胚胎的多能干细胞系，并将其命名为内细胞团干细胞（EpiSC），由于它们依赖碱性成纤维细胞生长因子-MAPK 和激活素 A-Smad2/3 信号来维持多能性，与小鼠胚胎干细胞（ESCs）不同，因此有望成为研究维持多能性机制的重要工具。此外，由于小鼠 EpiSCs 与人类 ESCs 之间存在相似性，因此 EpiSCs 有望成为人类干细胞治疗的有效实验模型。最近，人们对从 ESC 状态向 EpiSC 状态的转化或从 EpiSC 状态向 ESC 状态的逆转的研究引起了关注，因为这些技术可能会增加多能干细胞的潜力，并增加我们对其发育状态的了解。在本研究中，我们发现低氧浓度培养环境可加速、改善和稳定 Oct4ΔPE-GFP 转基因 ESCs 从 ESC 状态转化而来的 EpiSC 状态。低氧诱导的 EpiSCs（iEpiSCs）具有更接近的基因表达模式，并且 Stella 和 Oct4 基因启动子区域的亚硫酸氢盐序列表明，iEpiSC 在低氧条件下获得了 EpiSC 特异性的甲基化模式。我们的数据提供了证据表明，氧浓度是建立 EpiSC 特异性状态的一个重要因素。
