Healing mechanism of diabetic foot ulcers using single-cell RNA-sequencing.

BACKGROUND

Diabetic foot ulcer (DFU) is one of the common and severe complications in diabetic patients, mainly caused by the interaction of various factors such as peripheral neuropathy, peripheral vascular disease, and infection. Moreover, vascular damage, disorder of tissue cells, decreased expression level of neurotrophic factor, and decreased growth factor caused by long-term exposure to a high glucose environment can also lead to prolonged or incomplete wound healing. This imposes a tremendous financial burden on the patients' family and society. Although various innovative techniques and drugs have been developed to treat DFU, the therapeutic effect is still unsatisfactory.

METHODS

We filtered and downloaded the single-cell dataset of diabetic patients from the Gene Expression Omnibus (GEO) website and used the Seurat package in R for creation of single-cell objects, integration, control of quality, clustering, cell type identification, differential gene analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and intercellular communication analysis.

RESULTS

Diabetic healing-related differentially expressed gene (DEG) analysis showed that there were 1,948 differential genes between tissue stem cells in healing and non-healing wounds, of which 1,198 genes were up-regulated and 685 genes were down-regulated. The results of GO functional enrichment analysis in tissue stem cells showed that they were closely related to wound healing. The CCL2-ACKR1 signaling pathway activity in tissue stem cells influenced the biological activity of endothelial cell subpopulation, which ultimately promoted the healing of DFU wounds.

CONCLUSIONS

The CCL2-ACKR1 axis is closely associated with DFU healing.