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ATAC-seq of human dendritic cells

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE146896 | GEO | 2020/09/22

REPOSITORIES: GEO

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Project description:Dendritic cells (DCs) are a complex group of cells which play a critical role in vertebrate immunity. Spleen or lymph node resident DCs are subdivided into conventional DC (cDC) subsets (CD11b and CD8alpha in mouse; BDCA1 and BDCA3 in man) and plasmacytoid DCs (pDCs). It is currently unclear if these various DC populations belong to a unique hematopoietic lineage and if the subsets identified in the mouse and human systems are evolutionary homologs. To bring novel insights into these questions, we sought conserved genetic signatures for these DCs through the analysis of a compendium of genome-wide expression profiles of mouse or human leukocytes. We show through clustering analysis that all spleen resident DC subsets form a distinct branch within the leukocyte family tree, and reveal a transcriptomal signature evolutionary conserved in all these DC subsets. Moreover we identify a large gene expression program shared between mouse and human plasmacytoid DCs, and smaller conserved profiles shared between mouse and human cDC subsets. Finally, we use compendium analysis to re-evaluate the classification of interferon-producing killer DCs (IKDCs) and lin-CD16+HLA-DR+ cells, which have both been claimed to be DCs, and show that these cells are more closely linked to NK or myeloid cells, respectively. Our study thus provides a unique resource for future investigation of the evolutionarily conserved molecular pathways governing the ontogeny and functions of leukocyte subsets, especially DCs. Experiment Overall Design: This study includes data from cell sort purified dendritic cells, B cells, NK cells, and CD8 T cells. 2 or 3 independent replicates were made for each cell type. The genearray was performed in an attempt to investigate the relationships between DCs subsets and with other leukocytes, in mouse, in human, and between these 2 species. To this end, public data for mouse CD4 T cells and macrophages, as well as public data for human leukocyte subsets were also used in the analysis. The results have led to the identification of specific transcriptional programs conserved between human and mouse dendritic cell subsets.

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ATAC-seq of human dendritic cells

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