Temporal Dynamics of Endothelium After Radiation Injury Reveal a Transient Pro-Angiogenic Capillary Subpopulation Associated with Skin Repair

Ionizing radiation (IR) causes severe vascular damage, yet the dynamic functional states and regulatory mechanisms of vascular endothelial cells (VECs) after irradiation remain poorly understood. To elucidate the underlying processes, we analyzed single-cell RNA sequencing data from mouse dorsal skin collected at multiple post-irradiation (p.i.) time points using trajectory inference, pathway enrichment, transcription factor activity inference, and cell-cell communication analyses. Our results showed that VECs exhibited marked temporal dynamics after irradiation, transitioning from early-stage stress responses to middle-stage angiogenic remodeling and late-stage restoration of homeostasis. A transient <i>Gpihbp1</i>⁺ capillary endothelial subpopulation (capVEC2) emerged predominantly during the middle stage (2-3 days p.i.) and was enriched for angiogenesis- and migration-related programs. Enhanced Sp1 regulatory activity was associated with its pro-angiogenic phenotype. At 2 days p.i., capVEC2 engaged in pro-angiogenic and pro-repair signaling with keratinocytes, whereas by 3 days p.i. these interactions shifted toward immune surveillance and tissue homeostasis, accompanied by increased pro-inflammatory and pro-apoptotic signaling and a decline in capVEC2 abundance. Collectively, our findings identify a radiation-induced, transient functional endothelial subpopulation that is associated with vascular-epidermal communication during skin repair post irradiation.