浙江大学学报（医学版）2025，Vol.54Issue(5)：602-610,9.DOI:10.3724/zdxbyxb-2025-0464
糖尿病足溃疡皮肤组织免疫失调和巨噬细胞重编程单细胞转录组分析
Single-cell transcriptomic analysis reveals immune dysregula-tion and macrophage reprogramming in diabetic foot ulcers
摘要
Abstract
Objective:To elucidate the underlying mechanisms of macrophage-mediated inflammation and tissue injury in diabetic foot ulcer(DFU).Methods:Skin tissue samples were collected from patients with DFU and with non-DFU.A total of 79 272 high-quality cell transcriptomes were obtained using single-cell RNA sequencing.An unbiased clustering approach was employed to identify cell subpopulations.Seurat functions were used to identify differentially expressed genes between DFU and non-DFU groups,and gene ontology(GO)enrichment analysis was used to reveal gene function.Furthermore,cell-cell communication network construction and ligand-receptor interaction analysis were performed to reveal the mechanisms underlying cellular interactions and signaling regulation in the DFU microenvironment from multiple perspectives.Results:The results revealed a significant expansion of myeloid cells in DFU tissues,alongside a marked reduction in structural cells such as endothelial cells,epithelial cells,and smooth muscle cells.Major cell types underwent functional reprogramming,characterized by immune activation and impaired tissue remodeling.Specifically,macrophages in DFU skin tissues exhibited a shift toward a pro-inflammatory M1 phenotype,with upregulation of genes associated with inflammation and oxidative stress.Cell communication analysis further demonstrated that M1 macrophages served as both primary signal receivers and influencers in the COMPLEMENT pathway mediated communication network,and as key signal senders and mediators in the secreted phosphoprotein 1(SPP1)pathway mediated communication network,actively shaping the inflammatory microenvironment.Key ligand-receptor interactions driving macrophage signaling were identified,including C3-(ITGAM+ITGB2)and SPP1-CD44.Conclusions:This study establishes a comprehensive single-cell atlas of DFU,revealing the role of macrophage-driven cellular networks in chronic inflammation and impaired healing.These findings may offer potential novel therapeutic targets for DFU treatment.关键词
糖尿病足溃疡/单细胞RNA测序/巨噬细胞/组织重塑/免疫激活Key words
Diabetic foot ulcer/Single-cell RNA sequencing/Macrophage/Tissue remodeling/Immune activation分类
医药卫生引用本文复制引用
黄春丽,姜昱,焦伟,隋颖,王春雷,苏永涛..糖尿病足溃疡皮肤组织免疫失调和巨噬细胞重编程单细胞转录组分析[J].浙江大学学报（医学版）,2025,54(5):602-610,9.基金项目
山东省中医药科技项目(M20241812) This study was supported by Tradi-tional Chinese Medicine Science and Technology Project of Shandong Province(M20241812). （M20241812）
