Role of NR2F2-mediated reprogramming of endothelial cells in glioblastoma progression

Glioblastoma (GBM), a malignant brain tumor, is characterized by a high recurrence rate and poor overall survival. Therefore, understanding the causes of recurrence and identifying strategies for its prevention are crucial. To identify the characteristics of recurrent tumor samples and the molecular mechanisms of tumor progression, we conducted a longitudinal analysis of GBM using single-cell transcriptomics and clinical data from the Chinese Glioma Genome Atlas (CGGA). Compared to the primary tumor, recurrent GBM samples showed a more immunosuppressive environment. We identified an endothelial cell subpopulation, Edo4, that is characterized by high endothelial-to-mesenchymal transition (EMT) and is correlated with poor prognosis in recurrent tumors. It was regulated by the NR2F2 transcription factor specifically in the recurrent GBM samples. Cell-cell interaction analysis revealed that pericytes affect endothelial cell migration through the JAM2-(ITGA3+ITGB1) ligand-receptor axis, promoting GBM progression. Targeting the Edo4 cell cluster and the JAM2-(ITGA3+ITGB1) ligand-receptor pair may be a promising strategy to prevent GBM recurrence.