Single-cell transcriptomic analysis reveals immune dysregula-tion and macrophage reprogramming in diabetic foot ulcers.
10.3724/zdxbyxb-2025-0464
- Author:
Chunli HUANG
1
,
2
;
Yu JIANG
3
;
Wei JIAO
4
;
Ying SUI
4
;
Chunlei WANG
5
;
Yongtao SU
2
,
6
Author Information
1. School of Clinical Medicine, Shandong Second Medical University, Weifang 261053, Shandong Province, China. sunnyrabbit168@
2. com.
3. School of Clinical Medicine, Shandong Second Medical University, Weifang 261053, Shandong Province, China.
4. Institute of Tissue Regeneration and Wound Repair, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
5. Department of Burn Dermatology, PKUCare Luzhong Hospital, Zibo 255400, Shandong Province, China.
6. Institute of Tissue Regeneration and Wound Repair, Shandong University of Traditional Chinese Medicine, Jinan 250355, China. yongtaosu@
- Publication Type:Journal Article
- Keywords:
Diabetic foot ulcer;
Immune activation;
Macrophage;
Single-cell RNA sequencing;
Tissue remodeling
- MeSH:
Humans;
Macrophages/immunology*;
Diabetic Foot/pathology*;
Single-Cell Analysis;
Transcriptome;
Gene Expression Profiling;
Inflammation;
Skin;
Cell Communication;
Signal Transduction;
Cellular Reprogramming
- From:
Journal of Zhejiang University. Medical sciences
2025;54(5):602-610
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES: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.
