Shared gene signatures in keloid pathogenesis across ethnically diverse populations: Insights from scRNA-seq

Summary: Abstract Body: Keloids, pathological scars characterized by aberrant wound healing and excessive collagen deposition, are more prevalent in individuals with skin of color (SoC) and pose significant cosmetic and therapeutic challenges. This cross-sectional study aimed to uncover the molecular mechanisms underlying keloid formation using single-cell RNA sequencing (scRNA-seq). Keloid tissues from ten SoC patients, representing Asian, African American, Caucasian, and Hispanic populations, were analyzed alongside six normal skin controls. Analysis revealed 98 differentially expressed genes (DEGs) conserved across all ethnic groups, implicating critical biological processes in keloid pathogenesis. These include extracellular matrix organization (COL1A1,), inflammation (F2RL1), lipid metabolism (PLPP4), small leucine-rich proteoglycans (ASPN), the renin-angiotensin system (ACE), enzymatic activity (MMP11), and intracellular signaling pathways (MAPK11-12). The shared genetic signatures underscore the complex molecular interactions contributing to keloid development across ethnically diverse populations. Our findings underscore the importance of inclusive research to identify conserved molecular pathways in keloid pathogenesis and provide a robust foundation for developing targeted, effective therapies to improve clinical outcomes across diverse populations. Keshvad Hedayatyanfard¹, Alejandro Espinosa¹, Sarowar Jahan¹, Min Deng¹, Gregory M. Brewer¹, Priscila Andrade², Carol Cheng³, Alex Kheshvadjian³, Jeremy C Davis³, Matteo Pellegrini⁴, George W. Agak⁴ 1. Institute for Quantitative and Computational Biosciences - The Collaboratory, University of California, Los Angeles; Los Angeles, CA 90095, USA, Los Angeles, CA, United States. 2. Department of Molecular Cell and Developmental Biology, University of California Los Angeles; Los Angeles, CA 90095, USA, Los Angeles, CA, United States. 3. Dermatology, Division of Dermatology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles; Los Angeles, CA 90095, USA, Los Angeles, CA, United States. 4. Dermatology, Department of Molecular Cell and Developmental Biology, University of California Los Angeles; Los Angeles, CA 90095, USA, Los Angeles, CA, United States. Translational Studies: Cell and Molecular Biology