Chromatin Accessibility Landscapes of Skin Cells in Systemic Sclerosis Nominate Dendritic Cells in Disease Pathogenesis

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Nov 18

PMID 33203843

Citations 17

Authors

Qian Liu

Lisa C Zaba

Ansuman T Satpathy

Michelle Longmire

Wen Zhang

Kun Li

Jeffrey Granja

Chuang Guo

Jun Lin

Rui Li

Karen Tolentino

Gabriela Kania

Oliver Distler

David Fiorentino

Lorinda Chung

Kun Qu

Howard Y Chang

Affiliations

Soon will be listed here.

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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