ATACseq of 11 subsets of human postnatal developing thymocytes
The generation of TCRaß and TCR?d 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 ß-selection checkpoint is marked by transcriptional changes and a temporary increase in H3K27me3 without modifications in open chromatin, emerging ?d T cells, that originate from common precursors as ß-selected cells, show dramatic changes in chromatin accessibility which results from strong TCR signaling. Furthermore, we unravel distinct chromatin landscapes between CD4 and CD8 aß 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. Overall design: ATACseq of 11 ex-vivo sorted postnatal human thymocyte populations from two donors