Mitochondrial and transcription rate heterogeneity of mouse embryonic stem cells
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 <em>in vitro</em> and <em>in vivo</em>. Understanding the sources of this heterogeneity in p...
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| Format: | Thesis |
| Language: | English |
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2014
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| _version_ | 1817931882126376960 |
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| author | Gaál, B |
| author2 | Enver, T |
| author_facet | Enver, T Gaál, B |
| author_sort | Gaál, B |
| collection | OXFORD |
| description | 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 <em>in vitro</em> and <em>in vivo</em>. 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. |
| first_indexed | 2024-03-06T18:39:00Z |
| format | Thesis |
| id | oxford-uuid:0c416f1c-8f19-43c2-bb77-79ae00f41442 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:29:04Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:0c416f1c-8f19-43c2-bb77-79ae00f414422024-12-01T11:49:31ZMitochondrial and transcription rate heterogeneity of mouse embryonic stem cellsThesishttp://purl.org/coar/resource_type/c_db06uuid:0c416f1c-8f19-43c2-bb77-79ae00f41442BiologyStem cells (clinical sciences)EnglishOxford University Research Archive - Valet2014Gaál, BEnver, TNick, JBass, HCell-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 <em>in vitro</em> and <em>in vivo</em>. 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. |
| spellingShingle | Biology Stem cells (clinical sciences) Gaál, B Mitochondrial and transcription rate heterogeneity of mouse embryonic stem cells |
| title | Mitochondrial and transcription rate heterogeneity of mouse embryonic stem cells |
| title_full | Mitochondrial and transcription rate heterogeneity of mouse embryonic stem cells |
| title_fullStr | Mitochondrial and transcription rate heterogeneity of mouse embryonic stem cells |
| title_full_unstemmed | Mitochondrial and transcription rate heterogeneity of mouse embryonic stem cells |
| title_short | Mitochondrial and transcription rate heterogeneity of mouse embryonic stem cells |
| title_sort | mitochondrial and transcription rate heterogeneity of mouse embryonic stem cells |
| topic | Biology Stem cells (clinical sciences) |
| work_keys_str_mv | AT gaalb mitochondrialandtranscriptionrateheterogeneityofmouseembryonicstemcells |