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.
- MeSH
- aktivace lymfocytů genetika MeSH
- analýza hlavních komponent MeSH
- buněčná diferenciace imunologie MeSH
- buněčný rodokmen imunologie MeSH
- CD4-pozitivní T-lymfocyty cytologie imunologie MeSH
- CD8-pozitivní T-lymfocyty cytologie imunologie MeSH
- cytokiny metabolismus MeSH
- DNA vazebné proteiny metabolismus MeSH
- histokompatibilní antigeny metabolismus MeSH
- messenger RNA genetika metabolismus MeSH
- myši inbrední C57BL MeSH
- protein PEBP2A3 metabolismus MeSH
- receptory antigenů T-buněk metabolismus MeSH
- regulace genové exprese MeSH
- signální transdukce MeSH
- thymus cytologie imunologie MeSH
- transkripční faktory metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
