Single-cell profiling reveals transcriptomic signatures of vascular endothelial cells in non-healing diabetic foot ulcers

• DOI: 10.3389/fendo.2023.1275612
• Publication Date: 2023-12-04T08:18:30Z
• Authors: Yangzhou Lu; Xiaogang Liu; Jingling Zhao; Fan Bie; Yiling Liu; Julin Xie; Peng Wang; Junyou Zhu; Yahui Xiong; Shitian Qin; Fan Yang; Lei Chen; Yingbin Xu
• Keywords: 0301 basic medicine; Wound Healing; Gene Expression Profiling; Endothelial Cells; diabetic foot ulcers; RC648-665; single-cell RNA sequencing; Diseases of the endocrine glands. Clinical endocrinology; Diabetic Foot; 03 medical and health sciences; Endocrinology; inflammation; vascular endothelial cell; Diabetes Mellitus; Humans; immune; non-healing wounds; Skin

Background The treatment of diabetic foot ulcers (DFUs) poses a challenging medical problem that has long plagued individuals with diabetes. Clinically, wounds fail to heal for more than 12 weeks after the formation DFUs are referred as non-healing/chronic wounds. Among various factors contributing non-healing DFUs, impairment skin microvascular endothelial cell function caused by high glucose plays crucial role. Our study aimed reveal transcriptomic signatures cells, providing novel intervention targets strategies. Methods Based on GEO dataset (GSE165816), we selected DFU-Healer, DFU-Non-healer, and healthy non-diabetic controls research subjects. Single-cell RNA sequencing technology was employed analyze heterogeneity cells in different tissue samples identify healing-related subpopulations. Immunofluorescence applied validate results clinical specimens. Results number vascular density showed no significant differences among three groups However, from exhibited apparent inhibition angiogenesis, inflammation, immune-related signaling pathways. expression CCND1, ENO1, HIF1α, SERPINE1 significantly downregulated at histological levels. Further analysis demonstrated subpopulations limited connection other types weaker differentiation ability. Conclusion At single-cell level, uncovered molecular functional specificity highlighted importance immune-mediated capability angiogenesis wound healing. This provides new insights DFUs.