Tanaka Tetsuya S, Kunath Tilo, Kimber Wendy L, Jaradat Saied A, Stagg Carole A, Usuda Masayuki, Yokota Takashi, Niwa Hitoshi, Rossant Janet, Ko Minoru S H
Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, 21224-6820, USA.
Genome Res. 2002 Dec;12(12):1921-8. doi: 10.1101/gr.670002.
Large-scale gene expression profiling was performed on embryo-derived stem cell lines to identify molecular signatures of pluripotency and lineage specificity. Analysis of pluripotent embryonic stem (ES) cells, extraembryonic-restricted trophoblast stem (TS) cells, and terminally-differentiated mouse embryo fibroblast (MEF) cells identified expression profiles unique to each cell type, as well as genes common only to ES and TS cells. Whereas most of the MEF-specific genes had been characterized previously, the majority (67%) of the ES-specific genes were novel and did not include known differentiated cell markers. Comparison with microarray data from embryonic material demonstrated that ES-specific genes were underrepresented in all stages sampled, whereas TS-specific genes included known placental markers. Investigation of four novel TS-specific genes showed trophoblast-restricted expression in cell lines and in vivo, whereas one uncharacterized ES-specific gene, Esg-1, was found to be exclusively associated with pluripotency. We suggest that pluripotency requires a set of genes not expressed in other cell types, whereas lineage-restricted stem cells, like TS cells, express genes predictive of their differentiated lineage.
对胚胎来源的干细胞系进行了大规模基因表达谱分析，以确定多能性和谱系特异性的分子特征。对多能胚胎干细胞（ES细胞）、胚外限制滋养层干细胞（TS细胞）和终末分化的小鼠胚胎成纤维细胞（MEF细胞）进行分析，确定了每种细胞类型独特的表达谱，以及仅ES细胞和TS细胞共有的基因。虽然大多数MEF特异性基因先前已被鉴定，但ES特异性基因中的大多数（67%）是新发现的，且不包括已知的分化细胞标志物。与来自胚胎材料的微阵列数据比较表明，ES特异性基因在所有采样阶段的表达均不足，而TS特异性基因包括已知的胎盘标志物。对四个新发现的TS特异性基因的研究表明，它们在细胞系和体内均呈现滋养层限制表达，而一个未表征的ES特异性基因Esg-1被发现仅与多能性相关。我们认为，多能性需要一组在其他细胞类型中不表达的基因，而谱系受限的干细胞，如TS细胞，则表达预测其分化谱系的基因。
