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Characterizing Changes in the Transcriptional Networks underlying Pluripotency in Mouse Embryonic Stem Cells upon the Induction of Differentiation

Mouse embryonic stem cells (mESCs) are pluripotent cells capable of differentiating into all three germ layers present in the adult mouse. In this thesis, I have investigated the transcriptional changes that mESCs undergo as they are induced to differentiate towards the mesoderm lineage by 2i/LIF withdrawal and dimethyl sulfoxide (DMSO) treatment. 5 days of differentiation causes significant drops in expression of Sox2 and Oct4 primary transcript, while expression of Nanog and Kit significantly drops after only 1 day. It was determined that DMSO has no effect on the short-term changes in Nanog and Kit expression induced by 2i/LIF withdrawal. An expanded look at pluripotency-associated genes shows significant up-regulation of Oct4 and down-regulation of Klf4 and Stat3 following only 6 hours of 2i/LIF withdrawal. This data indicates that while some aspects of the transcriptional networks underlying pluripotency respond quickly to mesodermal differentiation cues, others remain unchanged for up to 5 days.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/33522
Date26 November 2012
CreatorsSchwartz, Michael Louis
ContributorsMitchell, Jennifer
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
Languageen_ca
Detected LanguageEnglish
TypeThesis

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