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Title: Mitochondrial and transcription rate heterogeneity of mouse embryonic stem cells
Author: Gaal, Bernadett
ISNI:       0000 0004 5359 0251
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2014
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Cell-to-cell variation in expression of pluripotency- and lineage-determining factors has been proposed to be integral to the process of cell fate commitment in pluripotent cells both in vitro and in vivo. Understanding the sources of this heterogeneity in pluripotent stem cells promises greater insight into the mechanisms underlying cell fate choice. I identify mitochondrial membrane potential as an axis of heterogeneity in mouse embryonic stem cell populations, and show that high mitochondrial membrane potential marks cells that are in a stable self-renewing state. Partial overlap with previously described metastable subpopulations is demonstrated through gene expression analysis. I present evidence that similarly to previous findings in HeLa, heterogeneity in mitochondrial membrane potential is associated with variation in global transcription rate in mESCs. The direct impact of global transcription rate on differentiation propensity is demonstrated through manipulation of RNA Pol II transcription elongation rate. Mitochondrial variability is therefore likely a functionally relevant source of extrinsic gene expression variability in mouse embryonic stem cells.
Supervisor: Enver, Tariq; Jones, Nick; Bass, Hassan Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biology ; Stem cells (clinical sciences) ; stem cells ; heterogeneity