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

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Title: The order and logic of CD4 CD8 lineage choice and differentiation in mouse thymus
Authors: Karimi, MM
Guo, Y
Cui, X
Pallikonda, HA
Horkova, V
Dore, MH
Wang, Y-F
Ruiz Gil, S
Rodriguez-Eteban, G
Robles Rebollo, I
Bruno, L
Georgieva, R
Patel, B
Elliott, J
Dauphars, D
Krangel, MS
Lenhard, B
Heyn, H
Fisher, AG
Stepanek, O
Merkenschlager, M
Item Type: Journal Article
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.
Issue Date: 4-Jan-2021
Date of Acceptance: 30-Oct-2020
URI: http://hdl.handle.net/10044/1/85325
DOI: 10.1038/s41467-020-20306-w
ISSN: 2041-1723
Publisher: Nature Research
Journal / Book Title: Nature Communications
Volume: 12
Copyright Statement: © The Author(s) 2020. This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third partymaterial in this article are included in the article’s Creative Commons license, unlessindicated otherwise in a credit line to the material. If material is not included in thearticle’s Creative Commons license and your intended use is not permitted by statutoryregulation or exceeds the permitted use, you will need to obtain permission directly fromthe copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: Wellcome Trust
Medical Research Council (MRC)
Funder's Grant Number: 099276/Z/12/Z
Publication Status: Published
Article Number: ARTN 99
Appears in Collections:Institute of Clinical Sciences
Faculty of Medicine

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