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Genome Folding and Nuclear Speckles Converge to Orchestrate Fibroblast Activation Zachary J. G Gardner
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Gardner, Zachary J. G., author.
- Language:
- English
- Subjects (All):
- 0369.
- 0487.
- 0758.
- Local Subjects:
- 0369.
- 0487.
- 0758.
- Physical Description:
- 1 electronic resource (114 pages)
- Contained In:
- Dissertations Abstracts International 87-07B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2025
- Language Note:
- English
- Summary:
- How cells balance identity stability with plasticity remains incompletely understood. Fibroblasts, which maintain tissue homeostasis and adopt diverse cell states, provide a model to study this balance. Genome organization coordinates gene expression, but how it directs changes in cellular identity remains unclear. We show that TGF-β rewires topologically associating domains and chromatin looping at upregulated genes. Cohesin was required for myofibroblast differentiation, while enhanced cohesin stability bypassed TGF-β signaling and drove a myofibroblast-like state. Given emerging evidence suggesting chromatin spatial positioning can tune gene expression, we examined the role of the nuclear speckle. Nuclear speckles were required for myofibroblast gene expression. Strikingly, enhancing genome folding partially rescued gene expression in fibroblasts with disrupted speckles. These findings advance our understanding of fibrosis and support a model in which distinct facets of genome organization must converge to orchestrate cell-state changes
- Notes:
- Advisors: Jain, Rajan; Kessler, Daniel S. Committee members: Blobel, Gerd A.; Joyce, Eric F.; Epstein, Jonathan A.; Wan, Liling
- Source: Dissertations Abstracts International, Volume: 87-07, Section: B.
- Ph.D. University of Pennsylvania 2025
- Vendor supplied data
- Local Notes:
- School code: 0175
- ISBN:
- 9798276001609
- Access Restriction:
- Restricted for use by site license
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