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Chromatin Landscape Underpinning Human Dendritic Cell Heterogeneity

Authors: Rebecca Leylek; Marcela Alcántara-Hernández; Jeffrey M. Granja; Michael Chavez; Kimberly Perez; Oscar R. Diaz; Rui Li; +3 Authors

Chromatin Landscape Underpinning Human Dendritic Cell Heterogeneity

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 analyze 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 uncover specific regions of chromatin accessibility for each subset and transcriptional regulators of DC function. By comparing plasmacytoid DC responses to IFN-I-producing and non-IFN-I-producing conditions, we identify genetic programs related to their function. Finally, by intersecting chromatin accessibility with genome-wide association studies, we recognize 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.

Keywords

Adult, Transcription, Genetic, QH301-705.5, CD40 Ligand, Polymorphism, Single Nucleotide, Article, Young Adult, Risk Factors, Humans, Genetic Predisposition to Disease, human, dendritic cells, Biology (General), Scleroderma, Systemic, pDCs, ATAC-seq, Dendritic Cells, Middle Aged, Chromatin, transitional dendritic cells, Repressor Proteins, Gene Expression Regulation, plasmacytoid dendritic cells, Chromatin Immunoprecipitation Sequencing, Genome-Wide Association Study

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    selected citations
    These citations are derived from selected sources.
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    25
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
25
Top 10%
Average
Top 10%
Green
gold