Edwards, YJK;
Bryson, K;
Jones, DT;
(2008)
A Meta-Analysis of Microarray Gene Expression in Mouse Stem Cells: Redefining Stemness.
PLOS ONE
, 3
(7)
, Article e2712. 10.1371/journal.pone.0002712.
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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 true for the proliferating adult SCs and the embryonic SCs.Conclusions/Significance: These findings suggest that looking at features associated with control of transcription is a promising future approach for characterizing "stemness'' and that further investigations of stemness could benefit from separate considerations of different SC states. For example, "proliferating-stemness'' is shown here, in terms of promoter usage, to be distinct from "quiescent-stemness''.
| Type: | Article |
|---|---|
| Title: | A Meta-Analysis of Microarray Gene Expression in Mouse Stem Cells: Redefining Stemness |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0002712 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0002712 |
| Language: | English |
| Additional information: | © 2008 Edwards et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by the Wellcome Trust Functional Genomics Initiative on Stem Cells (grant number: GR066745MA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/103184 |
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