ATAC-seq of human dendritic cells

Human dendritic cells (DCs) comprise subsets with distinct phenotypic and functional characteristics, but the transcriptional programs that dictate their identity remain elusive. Here, we collected global chromatin accessibility profiles across resting and stimulated human DC subsets by means of the assay for transposase-accessible chromatin using sequencing (ATAC-seq). We uncovered chromatin accessibility specific for each subset and discovered previously undescribed transcriptional regulators of DC function. By comparing responses of plasmacytoid DCs to type I interferon -producing and -not producing conditions, we identified genetic programs related to their function. Finally, by intersecting chromatin accessibility with genome-wide association studies, we recognized DC subset-specific enrichment of heritability in autoimmune diseases. Our results unravel the basis of human DC subset heterogeneity and provide a framework for their analysis in disease pathogenesis. Overall design: We performed ATAC-seq to measure chromatin accessibility in primary human dendritic cells (pDCs, cDC1, cDC2, CD11chi tDCs, CD11clo tDCs) and CD14+ monocytes, as well as stimulated pDCs.