The generation of TCR and TCR T cells proceeds through distinct developmental stages in which changing regulatory events control differentiation and lineage outcome. To clarify the underlying mechanisms, we employed RNAseq, ATACseq and ChIPmentation on well-defined thymocyte subsets that represent the continuum of human T cell development. The chromatin accessibility dynamics uncover stage-specific regulatory mechanisms and reveal that human T-lineage commitment is marked by the GATA3- and BCL11B-dependent closing of PU.1 sites. While the -selection checkpoint is marked by transcriptional changes and a temporary increase in H3K27me3 without modifications in open chromatin, emerging  T cells, that originate from common precursors as -selected cells, show dramatic changes in chromatin accessibility which results from strong TCR signaling. Furthermore, we unravel distinct chromatin landscapes between CD4 and CD8  T cells that support their effector functions and reveal gene-specific regulatory mechanism that define mature T cells. This resource provides an important framework for studying gene regulatory mechanisms that drive human normal and malignant T cell development. SOURCE: Juliette Roels (juliette.roels@ugent.be) -  Ghent University

Pluto Bioinformatics

GSE151080: RNAseq of ISP CD28+ cells stimulated with ImmunoCult