Intrathymic T-cell selection
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE2262 | GEO | 2005/03/07
SECONDARY ACCESSION(S): PRJNA91373
REPOSITORIES: GEO
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Project description:Comparisons between untreated primary cells T-cell precursors from the thymus. CD69- thymocytes are from Zap70-deficent mice and are >95% CD4+CD8+. These cells fail to generate intrathymic TCR signals as a result of their lacking Zap70 molecules, and are thus representative of "preselection" CD4+CD8+ thymocytes. The CD69hi population comes from wildtype mice and is heterogeneous for CD4 and CD8 expression. These cells have been intrathymically TCR-signaled and are undergoing selection.
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Project description:ab 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 mouse and human ab thymocyte developmental trajectories. We demonstrated asymmetric emergence of CD4+ and CD8+ lineages, matched differentiation programs of agonist-signaled cells to their MHC specificity, and identified correspondences between mouse and human transcriptomic and epigenomic patterns. 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. Our findings provide insight into the mechanisms of CD4+ and CD8+ T cell differentiation and a foundation for mechanistic investigations of ab T cell development.
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