Single-cell RNA sequencing reveals key molecular drivers of keloid persistence in skin of color 2406

Abstract Description Keloids are disproportionately prevalent among individuals with skin of color (SoC), yet transcriptome differences in SoC remain largely unexplored. In this study, we performed single-cell RNA sequencing on keloid tissues from ten individuals who developed post-acne keloids on their backs following severe acne. These individuals who self-identified as African-American, Hispanic, White or Asian were studied to uncover underlying gene expression differences in SoC. We identified genes associated with inflammation, proliferation, and fibrosis that were consistently upregulated across all donors. These genes were strongly linked to collagen production and extracellular matrix (ECM) remodeling, highlighting the roles of collagen deposition, cross-linking, and ECM stiffness in keloid pathology. Notably, certain matrix metalloproteinases were overexpressed in keloid tissue, driving selective ECM remodeling that enhances fibroblast survival and inhibits ECM degradation, thus contributing to keloid persistence in SoC. These findings provide critical insights into the molecular mechanisms of keloid formation in diverse skin types, offering a foundation for developing targeted treatments for individuals with understudied skin profiles. Funding Sources Supported by NIH grants R01AR081337 (GWA). Topic Categories Immune Mechanisms of Human Disease (HUM)