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Integration of Single Cell Transcriptomics and Epigenomics to Identify New Regulators of T Cell Development and Function / Laura Beth Chopp.
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Chopp, Laura Beth, author.
- Language:
- English
- Subjects (All):
- Immunology.
- Cellular biology.
- Genetics.
- Biophysics.
- Immunology--Penn dissertations.
- Penn dissertations--Immunology.
- Local Subjects:
- Immunology.
- Cellular biology.
- Genetics.
- Biophysics.
- Immunology--Penn dissertations.
- Penn dissertations--Immunology.
- Physical Description:
- 1 online resource (246 pages)
- Distribution:
- Ann Arbor : ProQuest Dissertations & Theses, 2022
- Contained In:
- Dissertations Abstracts International 84-02B.
- Place of Publication:
- [Philadelphia, Pennsylvania] : University of Pennsylvania, 2022.
- Language Note:
- English
- Summary:
- αβ lineage T cells, most of which are CD4+ or CD8+ and recognize MHC I or MHC II-presented antigens, are essential for immune responses and develop from CD4+CD8+ thymocytes. The absence of in vitro models and the heterogeneity of ab thymocytes have hampered analyses of their intrathymic differentiation. Here, combining single-cell RNA- and ATAC- (chromatin accessibility) sequencing, we identified conserved developmental trajectories for both mouse and human αβ thymocytes. Integrated analyses of MHC I- and MHC II-signaled cells demonstrated asymmetric emergence of CD4+ and CD8+ lineages. Through computational analysis of single cell data and binding sites for the CD4+-lineage transcription factor Thpok, we inferred transcriptional networks associated with CD4+- or CD8+-lineage differentiation, and with expression of Thpok or of the CD8+-lineage factor Runx3. Finally, we identified Zfp148 and Zfp281 as novel transcription factors that regulate CD4+ T cell development and function via cooperation with the transcription factor Gata3. Our findings provide new insights into the mechanisms of CD4+ and CD8+ T cell differentiation and CD4+ T cell function.
- Notes:
- Source: Dissertations Abstracts International, Volume: 84-02, Section: B.
- Advisors: Bosselut, Remy; Committee members: Allman, David; Belkaid, Yasmine; Henao-Mejia, Jorge; Speck, Nancy.
- Department: Immunology.
- Ph.D. University of Pennsylvania 2022.
- Local Notes:
- School code: 0175
- ISBN:
- 9798837504051
- Access Restriction:
- Restricted for use by site license.
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