PDCD10 loss is associated with inflammatory and barrier-related endothelial remodeling in cerebral cavernous malformation

Background PDCD10-associated cerebral cavernous malformations have an aggressive clinical presentation, but the accompanying endothelial responses remain incompletely defined. Methods We reanalyzed public single-cell transcriptomes from neonatal endothelial-specific Pdcd10-knockout and wild-type mice, with two mice per genotype. Vascular affiliation and pathological states were evaluated alongside mouse-level pseudobulk differential expression, pathway scores, shared pseudotime and predicted ligand–receptor communication. Independent mouse datasets and a pooled human vascular-organoid dataset assessed reproducibility and model dependence. Results Among 31,353 singlets, 27,445 endothelial-lineage candidates were retained for state mapping. The mean fraction of endothelial-to-mesenchymal-transition-like cells increased descriptively from 21.42% to 28.57%, with the largest increase in capillary-assigned cells. Pseudobulk analysis identified 682 differentially expressed genes, with enrichment of tumor necrosis factor–nuclear factor κB signaling and hypoxia. Serpine1 and Pgf increased, whereas Mfsd2a and Cldn5 decreased. The shared trajectory was branched and did not establish a universal endothelial-to-fibroblast sequence. Additional brain endothelial datasets reproduced Serpine1, Pgf and Fn1 increases, whereas cultured endothelial cells and organoids showed incomplete replication. Conclusions PDCD10 loss was associated with inflammatory and barrier-related endothelial remodeling. These exploratory findings nominate targets for tissue validation but do not establish lineage conversion, pathway specificity for PDCD10 loss or a causal explanation for human hemorrhage.