在人类诱导的多能干细胞中出现异常表观基因组重编程的热点
Ryan Lister1, Mattia Pelizzola, Yasuyuki S Kida
1Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Nature
|February 4, 2011
概括
诱导多能干细胞 (iPSCs) 在DNA甲基化重编程中表现出显著的变异性,保留体细胞记忆. 这些重编程签名即使在分化后也会持续存在,这影响了它们在再生医学中的使用.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 干细胞生物学 干细胞生物学
- 基因组学就是基因组学.
背景情况:
- 诱导多能干细胞 (iPSC) 是通过对体细胞进行重新编程来生成的,其目的是模仿胚胎干细胞 (ES) 进行再生医学.
- 表观基因组重构是这一过程的关键,但DNA甲基化模式恢复的完整性仍然不清楚.
研究的目的:
- 与ES细胞和体细胞相比,对人类iPSCs的全基因组DNA甲基化模式进行全面分析.
- 调查ES细胞样DNA甲基化恢复的程度,并确定潜在的重编程错误.
主要方法:
- 用单基因分辨率进行全基因组DNA甲基化分析,对5个人类iPSC线进行了分析.
- 对匹配的ES细胞,体细胞和差异化的iPSC/ES细胞的甲基组进行了分析以进行比较.
主要成果:
- 人类iPSC表现出显著的重编程变异性,包括保留的"体内记忆"和异常的DNA甲基化.
- 在共享的兆基量级中,离心体和端粒附近的差异甲基化区域表明非CG甲基化的不完全重编程.
- 在iPSC和ES细胞之间观察到CG甲基化和基因素修饰的差异.
结论:
- 重编程iPSC中的变异性导致ES细胞样DNA甲基化模式的不完全恢复.
- 在CG甲基化重编程中的错误经常在分化过程中传播,建立了一个持久的iPSC重编程签名.
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