1455 Identification and characterization of specific subsets in systemic sclerosis fibroblast cultures

Systemic sclerosis (SSc) is characterized by excessive deposition of extracellular matrix (ECM) in the involved organs. Fibroblasts are activated and develop an uncontrolled synthesis collagen other ECM constituents. Previous studies have focused on cultured fibroblasts, but interpretation results been limited due to possible selection fibroblast populations. To better understand heterogeneity SSc we conducted single cell RNA-sequencing (scRNA-seq) cells with aim 1) identify specific populations 2) be able explore potential new therapeutic targets. Our scRNA-seq analysis human dermal fibroblasts consisted 4 healthy donors. We identified numerous up- downregulated genes distinct A significant upregulation tetraspanin CD9 was seen most subsets when compared controls. Flow cytometry confirmed protein at surface fibroblasts. has previously linked exosomes our further functional revealed, knockout (KO) mouse embryonic a clear reduction I proteins level, thereby linking overexpression directly enhanced synthesis. Furthermore, strong Four Half LIM domains 1 (FHL1) detected small cluster RNA level. Although FHL1 implicated myofibroblast differentiation positive cultures did not correlate αSMA expressing subcluster thus established novel subpopulation