777 Overexpression of Vgll3 induces cutaneous fibrosis in a mouse model of lupus-like autoimmunity using single-cell RNA analyses

Fibrosis is characterized by collagen deposition, fibro/myofibroblast accumulation, and extracellular matrix remodeling. can be seen in autoimmune diseases where it may widespread affect organs beyond the skin, with high morbidity mortality, no effective treatment. In cutaneous lupus, scar formation after discoid lesion eruption evolve from enhanced fibrotic phenotypes. Our research has shown that epidermal-directed overexpression of murine Vgll3 causes severe lupus-like skin lesions suggestive lupus erythematosus (DLE). Given apparent nature transgenic (TG) mice, we wanted to determine if induces fibrosis. We analyzed male female TG wild-type (WT) mice aged 2-3 months. Fibrotic biomarkers human DLE scleroderma were analyzed. Epidermal resulted development not only inflammation, but also fibrosis significant expression found lesions. Overall, lesional exhibited higher Col1a1, Col1a2, Tgfb1 Ctgf. ScRNA-seq vs. WT demonstrated increased these genes was localized fibroblast (FB) myofibroblast populations. Four FB subclusters identified across all samples, one detected almost exclusively skin. This subcluster distinguished Tgfb1, Ly6c1 Eln. The presence this unique suggests epidermal impacts development, there a role for early