Single-cell analysis reveals fibroblast heterogeneity and myofibroblasts in systemic sclerosis-associated interstitial lung disease

Myofibroblasts are key effector cells in the extracellular matrix remodeling of systemic sclerosis-associated interstitial lung disease (SSc-ILD), however the diversity of fibroblast populations present in the healthy and SSc-ILD lung is unknown, and has prevented the specific study of the myofibroblast transcriptome. We sought to identify and define the transcriptomes of myofibroblasts and other mesenchymal cell populations in human healthy and SSc-ILD lungs to understand how alterations in fibroblast phenotypes lead to SSc-ILD fibrosis. We performed droplet-based single-cell RNA-sequencing with integrated canonical correlation analysis of 13 explanted lung tissue specimens (56,196 cells) from 4 healthy control and 4 SSc-ILD patients, with findings confirmed by cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) in additional samples. Please note that the control samples (GSM3660644-GSM3660648 in GSE128033) were re-used in the current study (as indicated in the GSM3666096-GSM3666100 sample titles). ***The GEO records contain only processed data (raw counts in sparse matrix format) as raw data is unavailable due to patient privacy concerns.