Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.601269
Title: Distinct transcriptional signatures of aneuploidy in murine pluripotent cell populations
Author: Skylaki, Stavroula
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2012
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Abstract:
Genomic integrity in mouse embryonic and induced pluripotent stem cells can be compromised by factors such as extended time in culture and cellular reprogramming. Surprising, only a few studies have thus far examined the accumulation of chromosomal imbalances in mouse pluripotent populations upon prolonged propagation in vitro. It is presumed that specific recurring genetic changes can confer selective growth advantage and resistance to apoptosis and/or differentiation to the affected cells, although the genes that drive these processes remain elusive. The presence of these changes in published studies can confound the analysis of the data and hinder the reproducibility of the results. At the transcriptional level, aneuploidy manifests as large chromosomal regions of aberrant gene expression. This thesis presents a method to identify these regions in large-scale datasets and interrogate for recurrent patterns. The present analysis shows that over half of the 315 mouse pluripotent samples examined carry whole or partial-chromosome spanning clusters of aberrant transcription. Furthermore, there are common gene expression changes across samples with any type of predicted aneuploidy and samples with chromosome-specific aberrations. These transcriptional signatures have been used to train classification models which can predict aneuploid samples with over 90% accuracy. This is an important step towards the development of a low-cost and reliable transcriptional validation assay for the presence of aneuploidy.
Supervisor: Wilson, Val; Tomlinson, Simon Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.601269  DOI: Not available
Keywords: Mouse pluripotent stem cells ; Aneuploidy ; Transcriptional clusters
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