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Stimulus Specificity of Trained Immune Memory in Human Macrophages Aoife O'Farrell
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- O'Farrell, Aoife, author.
- Language:
- English
- Subjects (All):
- 0202.
- 0369.
- 0423.
- 0982.
- Local Subjects:
- 0202.
- 0369.
- 0423.
- 0982.
- Physical Description:
- 1 electronic resource (152 pages)
- Contained In:
- Dissertations Abstracts International 87-07B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2025
- Language Note:
- English
- Summary:
- Cellular memory is a fundamental mechanism by which cells integrate information about past experiences to modulate future responses. However, our understanding of how these memories manifest at single-cell resolution and vary across stimuli remains limited. To address this gap, we developed quantitative frameworks for cellular memory across multiple systems, and applied these frameworks towards quantifying specificity of trained immune memory in human macrophages. First, using highly quantitative single-molecule RNA imaging of over 100,000 individual human macrophages, we revealed that trained immunity boosts inflammatory gene transcription through gene-specific mechanisms at the single cell level, and that any individual cell is capable of being trained. Next, we determined that different training stimuli generated distinct memory states, with long-term stimulus-dependent changes to epigenetic, transcriptomic, proteomic, and signalling compartments of trained cells. Collectively, our findings demonstrate that cells encode specific details about past experiences that influence future responses in a complex fashion, providing a preliminary foundation for future efforts to predict or engineer cell fate by exploiting mechanisms of cellular memory
- Notes:
- Advisors: Raj, Arjun Committee members: Lim, Bomyi; Shin, Sunny; Mir, Mustafa; Momin, Noor
- Source: Dissertations Abstracts International, Volume: 87-07, Section: B.
- Ph.D. University of Pennsylvania 2025
- Vendor supplied data
- Local Notes:
- School code: 0175
- ISBN:
- 9798276005676
- Access Restriction:
- Restricted for use by site license
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