a Department of Stem Cell Biology, School of Medicine , Konkuk University , Seoul 05029 , Korea.
b Center for Stem Cell Research , Institute of Advanced Biomedical Science, Konkuk University , Seoul 05029 , Korea.
Epigenetics. 2018;13(4):343-351. doi: 10.1080/15592294.2018.1460033. Epub 2018 May 3.
Genomic imprinting is the process of epigenetic modification whereby genes are expressed in a parent-of-origin dependent manner; it plays an important role in normal growth and development. Parthenogenetic embryos contain only the maternal genome. Parthenogenetic embryonic stem cells could be useful for studying imprinted genes. In humans, mature cystic ovarian teratomas originate from parthenogenetic activation of oocytes; they are composed of highly differentiated mature tissues containing all three germ layers. To establish human parthenogenetic induced pluripotent stem cell lines (PgHiPSCs), we generated parthenogenetic fibroblasts from ovarian teratoma tissues. We compared global DNA methylation status of PgHiPSCs with that of biparental human induced pluripotent stem cells by using Illumina Infinium HumanMethylation450 BeadChip array. This analysis identified novel single imprinted CpG sites. We further tested DNA methylation patterns of two of these sites using bisulfite sequencing and described novel candidate imprinted CpG sites. These results confirm that PgHiPSCs are a powerful tool for identifying imprinted genes and investigating their roles in human development and diseases.
基因组印迹是一种表观遗传修饰过程，在此过程中基因以亲本来源依赖的方式表达；它在正常生长和发育中起着重要作用。孤雌生殖胚胎仅含有母体基因组。孤雌生殖胚胎干细胞可用于研究印迹基因。在人类中，成熟的囊性卵巢畸胎瘤来源于卵母细胞的孤雌生殖激活；它们由高度分化的成熟组织组成，包含三个胚层。为了建立人类孤雌生殖诱导多能干细胞系（PgHiPSCs），我们从卵巢畸胎瘤组织中生成了孤雌生殖成纤维细胞。我们通过使用 Illumina Infinium HumanMethylation450 BeadChip 阵列比较了 PgHiPSCs 与双父母人类诱导多能干细胞的全基因组 DNA 甲基化状态。该分析确定了新的单印迹 CpG 位点。我们进一步使用亚硫酸氢盐测序测试了其中两个位点的 DNA 甲基化模式，并描述了新的候选印迹 CpG 位点。这些结果证实 PgHiPSCs 是鉴定印迹基因及其在人类发育和疾病中的作用的有力工具。
