Chromatin accessibility landscapes of skin cells in systemic sclerosis nominate dendritic cells in disease pathogenesis

Nature Communications
Qian LiuHoward Y Chang

Abstract

Systemic sclerosis (SSc) is a disease at the intersection of autoimmunity and fibrosis. However, the epigenetic regulation and the contributions of diverse cell types to SSc remain unclear. Here we survey, using ATAC-seq, the active DNA regulatory elements of eight types of primary cells in normal skin from healthy controls, as well as clinically affected and unaffected skin from SSc patients. We find that accessible DNA elements in skin-resident dendritic cells (DCs) exhibit the highest enrichment of SSc-associated single-nucleotide polymorphisms (SNPs) and predict the degrees of skin fibrosis in patients. DCs also have the greatest disease-associated changes in chromatin accessibility and the strongest alteration of cell-cell interactions in SSc lesions. Lastly, data from an independent cohort of patients with SSc confirm a significant increase of DCs in lesioned skin. Thus, the DCs epigenome links inherited susceptibility and clinically apparent fibrosis in SSc skin, and can be an important driver of SSc pathogenesis.

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Citations

Jul 29, 2021·Cell Stem Cell·Samantha B LarsenElaine Fuchs
Sep 5, 2021·Nature Reviews. Rheumatology·Pei-Suen TsouSteven O'Reilly

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Methods Mentioned

BETA
Assay
immunoprecipitation
biopsies
biopsy
FACS
flow-cytometry
flow cytometry
PCR

Software Mentioned

FlowJo
MACS2
preprocessCore
GREAT
HOMER
Genomica
pipe
HOMER scanMotifGenomeWide
bedtools
Bowtie

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