Single-cell RNA sequencing reveals the heterogeneity of endothelial cells in human dupuytren’s disease

Abstract Dupuytren's disease is a common localized fibrotic disorder that affects the palmar fascia. Recent research using single-cell RNA sequencing (scRNA-seq) has expanded our understanding of the main cellular and molecular processes in mesenchymal cells that drive Dupuytren's disease. However, the involvement of other cells in developing Dupuytren's disease is largely unresolved. Endothelial cells (ECs) play an important role in the pathophysiology of some fibrotic diseases, such as lung fibrosis, keloid, and systemic sclerosis, according to growing studies. In this study, scRNA-seq analysis from Dupuytren's disease, healthy dermis (DE), and nonpathogenic (Skoog's) fascia (SF) were performed to explore the major pathogenic ECs subpopulations associated with Dupuytren's disease. Our results showed that patients with Dupuytren's disease had a larger percentage of Endothelial cells with RGCC+ expression. We discovered the trajectory of differentiation from IL6+ ECs to RGCC+ ECs using RNA velocity and pseudotime analysis. Furthermore, utilizing integration analysis of DEG and hdWGCNA, the potential role of EC subpopulations involved in the disease was investigated. Finally, we identified potential endothelial cell transcription factors and investigated cell-cell communication among ECs. Overall, we discovered molecular features of ECs that relate to Dupuytren's disease at the single-cell level. These findings could contribute to our understanding of the pathogenesis of Dupuytren's disease.