Westbrook, Elizabeth Rose;
(2025)
Signalling and gene expression dynamics of a rapid cell state transition.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Cell state transitions require changes in gene expression, through co ordinated gain and loss of transcripts. How these transitions are co ordinated by cell populations during development is unclear. Single cell RNA sequencing of a continuous developmental population of Dic tyostelium revealed large-scale transcriptome remodelling, representing a ‘jump’ between functionally different cell states. Transcriptomic anal ysis revealed a signature of transcript upregulation in addition to large scale transcript loss at the jump. Both changes to the gene expression programme were investigated. Firstly, to investigate how cells use their signalling environment and upregulation of genes to navigate cell state transitions, we simultaneously imaged signalling and transcription of jump marker genes. Cells very early in development had weak, infre quent jump marker transcription, whereas cells later in development had strong, oscillatory transcription. Strong jump-associated transcrip tion coincided with cAMP signalling, the relay signal used to coordinate multicellular development. Strong transcription of jump genes depends on cAMP however different jump genes have different transcriptional responses to both endogenous and optogenetically-driven cAMP pulses. Secondly, to explore the dynamics of RNA loss in the context of the jump, I tagged a strongly downregulated transcript using the MS2-MCP sys tem. Using super-resolution imaging, I tracked living cells over time and measured their dynamic transcript changes. Imaging developing cells in their physiological context revealed that developmentally regu lated transcripts may have altered stability as cells transition between cell states. Widespread transcript loss paired with a coupling between signalling and transcription is a potentially powerful way to destabilise cell states and drive robust cell state transitions.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Signalling and gene expression dynamics of a rapid cell state transition |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2025. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10207086 |
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