Department of Ob/Gyn and Center for Reproductive Sciences, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143, USA.
Nat Cell Biol. 2011 May;13(5):541-9. doi: 10.1038/ncb2239. Epub 2011 Apr 17.
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.
人类诱导多能干细胞（iPS 细胞）与胚胎干细胞（ES 细胞）非常相似，但最近的报告表明，它们之间可能存在重要差异。我们对来自肝细胞（代表内胚层）、皮肤成纤维细胞（中胚层）和黑素细胞（外胚层）的人类 iPS 细胞进行了系统比较。所有分析的低传代 iPS 细胞都保留了原始细胞的转录记忆。体细胞基因的持续表达部分可以通过不完全启动子 DNA 甲基化来解释。这种表观遗传机制是 iPS 细胞中存在的一种稳健记忆的基础，这种记忆可以在使用不同方法（包括 RNA 转染）由多个实验室生成的 iPS 细胞中找到。未完全沉默的基因往往与在重编程过程中被抑制的其他基因隔离，这表明沉默机制在孤立基因上的招募可能效率低下。不完全重编程基因 C9orf64（9 号染色体开放阅读框 64）的敲低降低了人类 iPS 细胞生成的效率，表明体细胞记忆基因在重编程过程中可能具有功能相关性。
