Genetic tracing of thymic T cell differentiation
نویسندگان
چکیده
Abstract Thymic T cell differentiation is controlled by stereotyped processes that remain obscure. Here we develop a novel mouse genetic tool to trace thymic cells during antigen receptor (TCR) rearrangement. Briefly, insert inducible CreER into the Rag1 locus transiently expressed at early differentiation. In presence of Rosa reporters, Rag1-CreER mice enable us irreversibly label between double negative (DN) and positive (DP) stages upon acute tamoxifen treatment. physiological setting absence perturbations historically used investigate differentiation, our tracing in combination with flow cytometric measurement fates functional states maps kinetics, stoichiometry, fate determination cells. We further integrate experiments unbiased single RNA sequencing, TCR expression surface markers, linking dynamic gene expression. particular, show regulatory acquire CD73 over time as potential consequence persistent signaling lineage determinant Foxp3, marking maturation process commitment adaptation. Taken together, integrated resolves complex coupled alterations expression, selection, determination. Our results also serve foundation for exploration states, developmental pathways, drivers, modulators involved these crucial biological processes. R21 AI146614
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ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.219.05