Description
- Abstract:
- Aging is the one thing that no person has survived. This complex phenotype is driven by many changes, including an increased prevalence of cellular senescence. Senescent cells are in a characteristic state of proliferative arrest and drive nefarious aspects of aging such as inflammation and tissue damage. Furthermore, senescence is supported by many epigenetic alterations, including those at the large-scale level of genomic architecture. This thesis presents the highest resolution analysis of chromosome organization in cellular senescence to date. Many distinctive changes occur with senescence, such as an increase in chromatin looping associated with demethylation and derepression of retroelements at architecturally-supported “hotspots.” This thesis also presents improved tools to efficiently work with and compare genomic shape, namely the Chromosome Shape Alphabet method, which can identify prototypical shapes in the 3D genome, and TADBay, a new TAD calling method which is benchmarked as compared to other state-of-the-art callers. Lastly, this thesis presents a preliminary analysis of the single-cell epigenetic landscape of reprogramming, a new rejuvenation method, with an emphasis on the role of senescent cells. Overall, this research gives significant insight into how epigenetic changes, mainly at the level of genomic architecture, contribute to cellular senescence, bringing us closer towards living longer, healthier lives.
- Notes:
- Thesis (Ph. D.)--Brown University, 2024
Citation
Dalgarno, Audrey,
"Towards Understanding Functional Nuclear Alterations with Cellular Senescence"
(2024).
Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:jg2jde73/
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Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations
Theses and Dissertations for the Molecular Biology, Cell Biology, and Biochemistry department....