Comparison of the Transcriptomic Signatures of Skin and Lung Fibroblasts from Patients with Systemic Sclerosis

ABSTRACT: Systemic Sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis in connective tissues. Fibroblasts are the effector cells of fibrosis since they contribute to the production of collagen and other extracellular matrix components. The goal of this study is to compare the transcriptomic profiles of primary human SSc skin and SSc lung fibroblasts. First, we conducted a meta-analysis of differentially expressed (DE) genes from two previously published differential analyses (SSc vs. normal) using skin and lung fibroblasts, observing 8.7% overlap in DE genes and 30% overlap in impacted pathways. Next, we characterized the signature of several genes of interest from the pro- and anti-fibrotic programs within the unique and overlap groups and explored overlapping drugs that are predicted to revert DE genes to “normal expression”. Finally, we identified 3760 DE genes between SSc lung and SSc skin fibroblasts, highlighting that fibroblasts in the disease state carry a tissue-specific signature that should be taken into consideration for therapeutic development. We also identified core genes that can serve as common targets for both skin and lung in SSc. To our knowledge, this is the first study to describe overlapping genes and pathways in primary human skin and lung fibroblasts from SSc patients.