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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F21%3A00544970" target="_blank" >RIV/68378050:_____/21:00544970 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/s41467-020-20306-w" target="_blank" >https://www.nature.com/articles/s41467-020-20306-w</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-020-20306-w" target="_blank" >10.1038/s41467-020-20306-w</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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. Developing T cells commit to either CD4/helper or CD8/cytotoxic lineage in the thymus, but how CD4 and CD8 coreceptors and TCR signaling dictate this selection process is still unclear. Here the authors use single cell RNA sequencing of mouse thymocytes to show that, in selection intermediates, TCR signaling strength informs coreceptor expression timing.

Název v anglickém jazyce

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

Popis výsledku anglicky

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. Developing T cells commit to either CD4/helper or CD8/cytotoxic lineage in the thymus, but how CD4 and CD8 coreceptors and TCR signaling dictate this selection process is still unclear. Here the authors use single cell RNA sequencing of mouse thymocytes to show that, in selection intermediates, TCR signaling strength informs coreceptor expression timing.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature Communications

ISSN

2041-1723

e-ISSN

2041-1723

Svazek periodika

12

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

99

Kód UT WoS článku

000665636000026

EID výsledku v databázi Scopus

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