Integrative single-cell analysis of epigenomic and transcriptomic states in patients with systemic sclerosis-associated interstitial lung disease

Abstract

AbstractInterstitial lung disease is the primary cause of death in individuals who have systemic sclerosis, one of the autoimmune connective tissue diseases. Understanding the pathophysiology of the disease is crucial to developing treatment options. Here, we performed a single-cell multi-omic analysis on lung tissue samples from patients with systemic sclerosis-associated interstitial lung disease (SSC-ILD), profiling chromatin accessibility and gene expression in the same samples and discovering significant cellular heterogeneity. Systemic-venous endothelial cells (ECs) have been shown to be pro-inflammatory and highly active. In addition, it was shown that the transcription factor FOSL2 targets the genes involved in response to unfolded proteins in systemic-venous ECs. Furthermore, we prioritized functional risk variants for systemic sclerosis using a genome-wide association study. Ligand-receptor analysis revealed that ECs significantly increased interaction with B cells via CXCL10-CXCR3 in patients with SSC-ILD. Overall, our analysis emphasizes epigenetic and transcriptional patterns in systemic-venous ECs, which might be beneficial in understanding the pathogenesis of SSC-ILD.