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.

• Authors: Rebecca Leylek, Marcela Alcántara-Hernández, Jeffrey M Granja, Michael Chavez, Kimberly Perez, Oscar R Diaz, Rui Li, Ansuman T Satpathy, Howard Y Chang, Juliana Idoyaga
• Journal: Cell reports (Cell Rep) Vol. 32 Issue 12 Pg. 108180 (09 22 2020) ISSN: 2211-1247 [Electronic] United States
• PMID: 32966789 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Chromatin
• Repressor Proteins
• ZBTB18 protein, human
• CD40 Ligand

Topics

• Adult
• CD40 Ligand (metabolism)
• Chromatin (metabolism)
• Chromatin Immunoprecipitation Sequencing
• Dendritic Cells (metabolism)
• Gene Expression Regulation
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Humans
• Middle Aged
• Polymorphism, Single Nucleotide (genetics)
• Repressor Proteins (metabolism)
• Risk Factors
• Scleroderma, Systemic (genetics)
• Transcription, Genetic
• Young Adult