Stem Cell Unit, Institute of Life Sciences, The Hebrew University of Jerusalem, Israel ; Department of Genetics, Institute of Life Sciences, The Hebrew University of Jerusalem, Israel.
Stem Cell Unit, Institute of Life Sciences, The Hebrew University of Jerusalem, Israel ; Department of Genetics, Institute of Life Sciences, The Hebrew University of Jerusalem, Israel ; Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, 185 Cambridge Street, Boston, MA 02114, USA.
Stem Cell Reports. 2013 Dec 12;1(6):509-17. doi: 10.1016/j.stemcr.2013.11.007. eCollection 2013.
Molecular reprogramming of somatic cells into human induced pluripotent stem cells (iPSCs) is accompanied by extensive changes in gene expression patterns and epigenetic marks. To better understand the link between gene expression and DNA methylation, we have profiled human somatic cells from different embryonic cell types (endoderm, mesoderm, and parthenogenetic germ cells) and the iPSCs generated from them. We show that reprogramming is accompanied by extensive DNA methylation in CpG-poor promoters, sparing CpG-rich promoters. Intriguingly, methylation in CpG-poor promoters occurred not only in downregulated genes, but also in genes that are not expressed in the parental somatic cells or their respective iPSCs. These genes are predominantly tissue-specific genes of other cell types from different lineages. Our results suggest a role of DNA methylation in the silencing of the somatic cell identity by global nonspecific methylation of tissue-specific genes from all lineages, regardless of their expression in the parental somatic cells.
体细胞重编程为人类诱导多能干细胞（iPSCs）伴随着基因表达模式和表观遗传标记的广泛改变。为了更好地理解基因表达和 DNA 甲基化之间的联系，我们对来自不同胚胎细胞类型（内胚层、中胚层和孤雌生殖细胞）的人类体细胞和由其产生的 iPSCs 进行了分析。我们发现，重编程伴随着 CpG 贫乏启动子的广泛 DNA 甲基化，而 CpG 丰富启动子则幸免。有趣的是，CpG 贫乏启动子中的甲基化不仅发生在下调基因中，也发生在亲本体细胞或其各自的 iPSCs 中不表达的基因中。这些基因主要是来自不同谱系的其他细胞类型的组织特异性基因。我们的结果表明，DNA 甲基化在通过所有谱系的组织特异性基因的全局非特异性甲基化沉默体细胞身份方面发挥作用，而与亲本体细胞中的表达无关。
