Decoding the Spatiotemporal Dynamics of ENTPD1 in Diabetic Foot Ulcer Through Multi-Omic Profiling.

Area of Science:

• Biomedical Research
• Molecular Biology
• Genomics

Background:

• Diabetic foot ulcers (DFUs) incidence is rising globally with diabetes mellitus.
• The role of extracellular nucleotidase ENTPD1 (CD39) in DFU pathogenesis is unclear.
• ENTPD1 is associated with immunogenic cell death (ICD).

Purpose of the Study:

• To investigate the role of ENTPD1 in DFU healing.
• To identify genetic, functional, and communication differences in DFUs versus healthy subjects.
• To explore molecular mechanisms of DFU healing and secondary diabetic peripheral artery disease (DPAD).

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of DFU and healthy tissues.
• Re-clustering of vascular endothelial cells (Vasendo) to identify ENTPD1+ subtypes.
• Cell communication analysis, eQTL Mendelian randomization, and bulk sequencing validation.

Main Results:

• Higher ICD levels and ENTPD1 expression correlated with DFU healing.
• ENTPD1+ Vasendo demonstrated healing-promoting effects in DFUs.
• Specific gene expression changes in Vasendo were linked to DFU healing and secondary DPAD risk.

Conclusions:

• ENTPD1+ Vasendo play a crucial role in DFU healing.
• Molecular mechanisms for DFU healing and secondary DPAD have been elucidated.
• Identified potential therapeutic targets for DFU and DPAD treatment.