Shovlin Tanya C, Durcova-Hills Gabriela, Surani Azim, McLaren Anne
The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.
Dev Biol. 2008 Jan 15;313(2):674-81. doi: 10.1016/j.ydbio.2007.11.007. Epub 2007 Nov 17.
Pluripotent stem cells, termed embryonic germ (EG) cells, have been generated from both human and mouse primordial germ cells (PGCs). Like embryonic stem (ES) cells, EG cells have the potential to differentiate into all germ layer derivatives and may also be important for any future clinical applications. The development of PGCs in vivo is accompanied by major epigenetic changes including DNA demethylation and imprint erasure. We have investigated the DNA methylation pattern of several imprinted genes and repetitive elements in mouse EG cell lines before and after differentiation. Analysed cell lines were derived soon after PGC specification, "early", in comparison with EG cells derived after PGC colonisation of the genital ridge, "late" and embryonic stem (ES) cell lines, derived from the inner cell mass (ICM). Early EG cell lines showed strikingly heterogeneous DNA methylation patterns, in contrast to the uniformity of methylation pattern seen in somatic cells (control), late EG cell and ES cell lines. We also observed that all analysed XX cell lines exhibited less methylation than XY. We suggest that this heterogeneity may reflect the changes in DNA methylation taking place in the germ cell lineage soon after specification.
多能干细胞，即胚胎生殖（EG）细胞，已从人类和小鼠的原始生殖细胞（PGC）中产生。与胚胎干细胞（ES）一样，EG细胞有分化为所有胚层衍生物的潜力，对未来的任何临床应用也可能很重要。PGC在体内的发育伴随着主要的表观遗传变化，包括DNA去甲基化和印记消除。我们研究了小鼠EG细胞系在分化前后几个印记基因和重复元件的DNA甲基化模式。与从生殖嵴PGC定殖后获得的EG细胞（“晚期”）以及从内细胞团（ICM）获得的胚胎干细胞（ES）细胞系相比，分析的细胞系是在PGC特化后不久获得的，即“早期”。与体细胞（对照）、晚期EG细胞和ES细胞系中甲基化模式的一致性相比，早期EG细胞系表现出显著的异质性DNA甲基化模式。我们还观察到，所有分析的XX细胞系的甲基化程度均低于XY细胞系。我们认为，这种异质性可能反映了特化后不久生殖细胞谱系中发生的DNA甲基化变化。
