a meta-analysis of microarray gene expression in mouse stem cells redefining stemness微阵列基因表达的荟萃分析老鼠干细胞具备干细胞重新定义.pdfVIP

A Meta-Analysis of Microarray Gene Expression in Mouse Stem Cells: Redefining Stemness Yvonne J. K. Edwards, Kevin Bryson, David T. Jones* Bioinformatics Group, Department of Computer Science, University College London, London, United Kingdom Abstract Background: While much progress has been made in understanding stem cell (SC) function, a complete description of the molecular mechanisms regulating SCs is not yet established. This lack of knowledge is a major barrier holding back the discovery of therapeutic uses of SCs. We investigated the value of a novel meta-analysis of microarray gene expression in mouse SCs to aid the elucidation of regulatory mechanisms common to SCs and particular SC types. Methodology/Principal Findings: We added value to previously published microarray gene expression data by characterizing the promoter type likely to regulate transcription. Promoters of up-regulated genes in SCs were characterized in terms of alternative promoter (AP) usage and CpG-richness, with the aim of correlating features known to affect transcriptional control with SC function. We found that SCs have a higher proportion of up-regulated genes using CpG-rich promoters compared with the negative controls. Comparing subsets of SC type with the controls a slightly different story unfolds. The differences between the proliferating adult SCs and the embryonic SCs versus the negative controls are statistically significant. Whilst the difference between the quiescent adult SCs compared with the negative controls is not. On examination of AP usage, no difference was observed between SCs and the controls. However, comparing the subsets of SC type with the controls, the quiescent adult SCs are found to up-regulate a larger proportion of genes that have APs compared to the controls and the converse is tr