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Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells.( o$ o! T/ U" q
Ohi Y, Qin H, Hong C, Blouin L, Polo JM, Guo T, Qi Z, Downey SL, Manos PD, Rossi DJ, Yu J, Hebrok M, Hochedlinger K, Costello JF, Song JS, Ramalho-Santos M.+ L/ v1 [3 p9 f& m
Source1] Departments of Ob/Gyn and Pathology and Center for Reproductive Sciences, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143, USA [2] Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, 35 Medical Center Way, San Francisco, California 94143, USA [3] Diabetes Center, University of California, San Francisco, California 94143, USA [4].
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Abstract
, d1 x! }1 S7 [. }Human induced pluripotent stem (iPS) cells are remarkably similar to embryonic stem (ES) cells, but recent reports indicate that there may be important differences between them. We carried out a systematic comparison of human iPS cells generated from hepatocytes (representative of endoderm), skin fibroblasts (mesoderm) and melanocytes (ectoderm). All low-passage iPS cells analysed retain a transcriptional memory of the original cells. The persistent expression of somatic genes can be partially explained by incomplete promoter DNA methylation. This epigenetic mechanism underlies a robust form of memory that can be found in iPS cells generated by multiple laboratories using different methods, including RNA transfection. Incompletely silenced genes tend to be isolated from other genes that are repressed during reprogramming, indicating that recruitment of the silencing machinery may be inefficient at isolated genes. Knockdown of the incompletely reprogrammed gene C9orf64 (chromosome 9 open reading frame 64) reduces the efficiency of human iPS cell generation, indicating that somatic memory genes may be functionally relevant during reprogramming., u$ n) L% x, t# V; F4 c
9 d( b: q9 v7 t# ?9 U' rPMID: 21499256 [PubMed - as supplied by publisher] $ i: d& `1 F8 `2 B# b+ a
人类的iPS与ESC显著相似，但是最近报道表明它们之间可能有十分重要的差异。本文对肝细胞（内胚层代表物）来源的iPS、表皮成纤维（中胚层）来源的iPS与黑色素（外胚层）来源的iPS进行了系统的比较。低代数的iPS分析保有原始细胞的转录记忆。体细胞的持续表达可以用启动子DNA的不完全甲基化做部分解释。这种形成强烈记忆的基础的表观机制可以由不同实验室使用不方法（包括RNA转染）获得的iPS中发现。不完整的基因沉默能在重编程中受抑制的基因中分离，表明沉默机制的募集在所进行分离的基因中是低效地。不完全重编程的基因C9orf64（染色体9上的开放阅读框64） 的敲低降低了iPS产生的效率，表明体细胞记忆基因在功能上与重编程相关。
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发表于 2011-4-23 12:45
发表于 2011-4-23 12:56
