The order and logic of CD4 versus CD8 lineage choice and differentiation in mouse thymus

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• dc.contributor.author Karimi, Mohammad M.
• dc.contributor.author Ruiz Gil, Sara
• dc.contributor.author Rodríguez Esteban, Gustavo
• dc.contributor.author Merkenschlager, Matthias
• dc.date.accessioned 2022-06-07T09:06:04Z
• dc.date.available 2022-06-07T09:06:04Z
• dc.date.issued 2021
• dc.description.abstract CD4 and CD8 mark helper and cytotoxic T cell lineages, respectively, and serve as coreceptors for MHC-restricted TCR recognition. How coreceptor expression is matched with TCR specificity is central to understanding CD4/CD8 lineage choice, but visualising coreceptor gene activity in individual selection intermediates has been technically challenging. It therefore remains unclear whether the sequence of coreceptor gene expression in selection intermediates follows a stereotypic pattern, or is responsive to signaling. Here we use single cell RNA sequencing (scRNA-seq) to classify mouse thymocyte selection intermediates by coreceptor gene expression. In the unperturbed thymus, Cd4+Cd8a- selection intermediates appear before Cd4-Cd8a+ selection intermediates, but the timing of these subsets is flexible according to the strength of TCR signals. Our data show that selection intermediates discriminate MHC class prior to the loss of coreceptor expression and suggest a model where signal strength informs the timing of coreceptor gene activity and ultimately CD4/CD8 lineage choice.
• dc.description.sponsorship Funding: the Medical Research Council, UK (B.L., A.G.F., M.M.), the Wellcome Trust (Investigator Award 099276/Z/12/Z to M.M.), the National Institutes of Health (NIH 1R35GM136284 to M.K.), and the Swiss National Science Foundation (SNSF Promys IZ11Z0_166538 to O.S.)
• dc.format.mimetype application/pdf
• dc.identifier.citation Karimi MM, Guo Y, Cui X, Pallikonda HA, Horková V, Wang YF et al. The order and logic of CD4 versus CD8 lineage choice and differentiation in mouse thymus. Nat Commun. 2021 Jan 4;12(1):99. DOI:10.1038/s41467-020-20306-w
• dc.identifier.doi http://dx.doi.org/10.1038/s41467-020-20306-w
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/53398
• dc.language.iso eng
• dc.publisher Nature Research
• dc.rights © Mohammad M. Karimi et al. 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.other Genètica
• dc.subject.other Expressió gènica
• dc.title The order and logic of CD4 versus CD8 lineage choice and differentiation in mouse thymus
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion