Reduced Oxygen Concentration Enhances Conversion of Embryonic Stem Cells to Epiblast Stem Cells
Reduced Oxygen Concentration Enhances Conversion of Embryonic Stem Cells to Epiblast Stem Cells
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DOI：
10.1089/scd.2011.0322
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发表时间：
2012-05-01
影响因子：
4
通讯作者：
Fukuda, Kanji
中科院分区：
文献类型：
--
作者：
Takehara, Toshiyuki;Teramura, Takeshi;Fukuda, Kanji
最近，来自小鼠胚胎的另一种类型的多能干细胞系已经建立，并被称为外胚层干细胞（EpiSC），并且有望成为研究多能性维持机制的重要工具，因为它们依赖于基本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。此外，由于小鼠EpiSCs和人类ESCs之间的相似性，EpiSCs有望成为人类干细胞治疗的有效实验模型。最近，从ESC状态到EpiSC状态的转化或从EpiSC状态到ESC状态的逆转的研究引起了人们的兴趣，因为这些技术可能会增加多能干细胞的潜力和我们对其发育状态的了解。在本研究中，我们发现低氧培养环境加速、改善和稳定了Oct4 Delta PE-GFP转基因ESCs从ESC状态转化细胞的EpiSC状态。缺氧条件下诱导的EpiSCs （iEpiSCs）具有与天然EpiSCs更接近的基因表达模式，Stella和Oct4基因启动子区域的亚硫酸盐序列表明，iEpiSC在缺氧条件下获得EpiSCs特异性甲基化模式。我们的数据证明氧浓度是episcc特异性状态建立的重要因素。
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 Oct4 Delta PE-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.