Epigenetic-scale comparison of human iPSCs generated by retrovirus, Sendai virus or episomal vectors
Epigenetic-scale comparison of human iPSCs generated by retrovirus, Sendai virus or episomal vectors
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DOI：
10.1016/j.reth.2018.08.002
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发表时间：
2018-12-01
影响因子：
4.3
通讯作者：
Umezawa, Akihiro
中科院分区：
文献类型：
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作者：
Nishino, Koichiro;Arai, Yoshikazu;Umezawa, Akihiro
人诱导多能干细胞（iPSC）是通过引入多种重编程因子（如 OCT3/4、SOX2、KLF4、c-MYC）建立的。由于其多能性和永生性，iPSC 被认为是再生医学的强大工具。迄今为止，世界各地已通过各种基因传递方法建立了 iPSC。所有方法均诱导出高质量的 iPSC，但尚未对基因递送方法差异引起的异常进行表观遗传学分析。在这里，我们使用逆转录病毒、仙台病毒和附加型载体三种载体从经血细胞中产生了基因匹配的人类 iPSC，并比较了它们之间的全基因组 DNA 甲基化谱。尽管异常甲基化的比较表明，仙台病毒载体产生的iPSC在三种载体中具有最少数量的异常甲基化位点，但非整合方法产生的iPSC并未表现出载体特异性的异常甲基化。然而，iPSC 系之间的差异被确定为与胚胎干细胞相比随机异常高甲基化区域的数量。这些随机异常的高甲基化可能是每个 iPSC 系特性差异的原因。 (C) 2018，日本再生医学会。由 Elsevier B.V. 制作和主持
Human induced pluripotent stem cells (iPSCs) are established by introducing several reprogramming factors, such as OCT3/4, SOX2, KLF4, c-MYC. Because of their pluripotency and immortality, iPSCs are considered to be a powerful tool for regenerative medicine. To date, iPSCs have been established all over the world by various gene delivery methods. All methods induced high-quality iPSCs, but epigenetic analysis of abnormalities derived from differences in the gene delivery methods has not yet been performed. Here, we generated genetically matched human iPSCs from menstrual blood cells by using three kinds of vectors, i.e., retrovirus, Sendai virus, and episomal vectors, and compared genome-wide DNA methylation profiles among them. Although comparison of aberrant methylation revealed that iPSCs generated by Sendai virus vector have lowest number of aberrant methylation sites among the three vectors, the iPSCs generated by non-integrating methods did not show vector-specific aberrant methylation. However, the differences between the iPSC lines were determined to be the number of random aberrant hypermethylated regions compared with embryonic stem cells. These random aberrant hypermethylations might be a cause of the differences in the properties of each of the iPSC lines. (C) 2018, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.