Single-cell transcriptomic analyses unveil exercise-induced changes in murine skin vascular endothelial cells

Physical activity (PA) is a fundamental aspect of preventive medicine, offering profound benefits for cardiovascular health and overall well-being. Despite its widespread benefits, the molecular mechanisms underlying PA-induced improvements in microvascular functions remain poorly understood. The skin microvasculature is uniquely affected by exercise-induced shear stress, especially during thermoregulation. Using single-cell RNA sequencing, we investigated how voluntary exercise influences the transcription profile of endothelial cells in the skin microvasculature of mice. We assigned 20 mice to either a sedentary group or a 1-month voluntary exercise program involving running wheels. Post-intervention, we collected skin biopsies from twelve mice for transcriptomic analyses. The differential expression analysis showed a significant increase in the expression of the Zbtb16 gene in vascular endothelial cells (vECs). The expression of Zbtb16 in vECs was correlated with genes involved in angiogenesis. Additionally, Gene Set Enrichment Analysis (GSEA) with nominally differentially expressed genes in vECs highlighted the suppression of pathways related to oxidative stress, cell proliferation and metabolism in the exercise group. This suggests an exercise-triggered transition towards improved metabolic efficiency and enhanced homeostasis in vECs. These results begin to reveal how exercise induces molecular changes in vECs of the skin microvasculature, highlighting PA's role in influencing endothelial function. Overall design: Single cells were isolated from mice subjected to physical activity and from sedentary controls. Libraries were prepared using the 10x Genomics Chromium single-cell RNA-sequencing (scRNA-seq) protocol.