Epigenetic regulation of profibrotic macrophages in systemic sclerosis- associated interstitial lung disease

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is the leading cause of death in patients with systemic sclerosis (SSc) with unclear pathogenesis and limited treatment options. Evidence strongly supports an important role for profibrotic, SPP1-expressing macrophages in SSc-ILD. We sought to define the transcriptome and chromatin structural changes of SPP1 SSc-ILD macrophages, so as to better understand their role in promoting fibrosis and to identify transcription factors associated with open chromatin driving their altered phenotype. Overall design: We performed single cell RNA-sequencing on 11 explanted SSc-ILD and healthy control lung samples, as well as single cell ATAC-sequencing on a subset of lung samples to define altered chromatin accessibility of SPP1 macrophages. We predicted transcription factors regulating SPP1 macrophages using SCENIC and determined transcription factor binding sites associated with global alterations in SPP1 chromatin accessibility using Signac/Seurat.