Single-cell RNA sequencing in diabetic foot ulcers: pathogenesis, biomarkers, and translational potential

Diabetic foot ulcer (DFU), a common diabetic complication driven by impaired angiogenesis, neuropathy and metabolic disorders, has complex pathogenesis and poses great challenges to clinical management. Single-cell RNA sequencing (scRNA-seq), an emerging transcriptomic technique, allows disease profiling at single-cell resolution. This review summarizes recent advances in scRNA-seq-based DFU research, revealing that JMJD3-mediated macrophage polarization failure and dysregulated IGF-1-SP1-CD248 pathway hinder wound repair, with MMP1, MMP3, MMP11 , JMJD3 and HIF1A identified as valuable biomarkers and therapeutic targets. It highlights scRNA-seq’s utility in unraveling pathogenic mechanisms, discovering therapeutic targets and biomarkers, and facilitating precision medicine, to provide new insights and research directions for DFU therapy.