Pre-existing chromatin accessibility and gene expression differences among naive CD4+ T cells influence effector potential

Dakota Rogers

doi:10.1016/j.celrep.2021.110064

Pre-existing chromatin accessibility and gene expression differences among naive CD4+ T cells influence effector potential

2021-11-01

22

OA

AI

Jasper J. P. van Beek

Stephanie A. Condotta

DOI：10.1016/j.celrep.2021.110064

Original

Save

View PDF

Abstract

En 中文

CD4(+) T cells have a remarkable potential to differentiate into diverse effector lineages following activation. Here, we probe the heterogeneity present among naive CD4(+) T cells before encountering their cognate antigen to ask whether their effector potential is modulated by pre-existing transcriptional and chromatin landscape differences. Single-cell RNA sequencing shows that key drivers of variability are genes involved in T cell receptor (TCR) signaling. Using CD5 expression as a readout of the strength of tonic TCR interactions with self-peptide MHC, and sorting on the ends of this self-reactivity spectrum, we find that pre-existing transcriptional differences among naive CD4(+) T cells impact follicular helper T (T-FH) cell versus non-T-FH effector lineage choice. Moreover, our data implicate TCR signal strength during thymic development in establishing differences in naive CD4(+) T cell chromatin landscapes that ultimately shape their effector potential.

Keywords:

TRANSCRIPTION FACTORS

POSITIVE SELECTION

CD5 EXPRESSION

TCR SIGNALS

HELPER

SELF

REPERTOIRE

FOREIGN

HETEROGENEITY

QUIESCENCE

Pre-existing chromatin accessibility and gene expression differences among naive CD4+ T cells influence effector potential

Abstract

AI Summary

Journal

Organization