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BackgroundWound healing is a complex, highly regulated process that is critical for restoring the anatomic and functional integrity of the skin after injury, which requires the interaction of various cell types. During acute wound healing, epidermal cells will activate at precise temporal stages, and proper communication will occur between different cells and will restore the skin integrity eventually. However, why the chronic wounds stagnate in an undefined non-healing state and how the epidermal cells interact with each other in the chronic wound environment is still unclear. To provide new insights into chronic wound healing, we reconstructed the variations in the epidermal cell-cell communication network that occur in chronic wound healing via single-cell RNA-seq (scRNA-seq) data analysis. MethodsWe used the count matrix of scRNA-seq data to create a Seurat object with the R package “Seurat” which was analyzed using default parameters. GO analysis was performed for the differentially expressed genes with Enrichr by R package “Cluster Profiler”. Then we created a CellChat object with the R package “CellChat” from Seurat and reconstructed the cell-cell autocrine and paracrine signaling interactions through CellChatDB.ResultsSix cell types are annotated in each wound type and through comparing the acute and chronic wounds we found that cellular and molecular interactions of epidermal cells are enhanced in chronic wounds. Especially, the PTN and PAR signaling pathways were significantly changed in chronic wounds. Then we found the melanocyte cell population was the dominant sender of PTN and PAR signaling pathways and the most contributing ligand-receptor pairs of the PTN and PAR signaling pathways were PTN-SDC1 and CTSG-F2RL1 respectively. ConclusionsIn this study, we used CellChat to reconstruct the epidermal cell-cell autocrine and paracrine signaling networks and try to understand the underlying molecular and physiological perturbations in non-healing wounds. we speculate that melanocytes may play a key role in skin regeneration, and that the absence of the PTN pathway and increasing PAR signaling pathways may disrupt the healing in chronic wounds. In addition, we identified that CTSG and PTN may respectively be a novel potential target and a therapeutic strategy in the treatment of chronic wounds. |
