Chromatin Landscape Underpinning Human Dendritic Cell Heterogeneity
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
Affiliations
Rebecca Leylek
Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Immunology Program, Stanford University School of Medicine, Stanford, CA 94305, USA
Marcela Alcántara-Hernández
Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Immunology Program, Stanford University School of Medicine, Stanford, CA 94305, USA
Jeffrey M. Granja
Biophysics Program, Stanford University School of Medicine, Stanford, CA 94305, USA; Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA 94305, USA
Michael Chavez
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
Kimberly Perez
Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Immunology Program, Stanford University School of Medicine, Stanford, CA 94305, USA
Oscar R. Diaz
Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
Rui Li
Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA 94305, USA
Ansuman T. Satpathy
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
Howard Y. Chang
Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA
Juliana Idoyaga
Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Immunology Program, Stanford University School of Medicine, Stanford, CA 94305, USA; Corresponding author
Summary: 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.
