CD157+ vascular endothelial stem cells represent a conserved subpopulation with an angiogenic gene expression profile

Summary Endothelial cells expressing the CD157 antigen (CD157+ ECs) contribute to vascular regeneration and maintenance in adult tissues, but their molecular identity is not fully defined. Here, we show that CD157-positive ECs in mouse and human tissues share conserved transcriptional profiles enriched for angiogenesis-associated genes. Regulon analysis revealed a gene-regulatory network in which the NFAT pathway contributes to vascular network formation. Integration of mouse and human scRNA-seq datasets revealed human EC clusters with gene expression profiles resembling mouse CD157-positive ECs. The clusters were localized in the large vessel intima and expressed known stem-like EC markers such as BST1 (CD157), PROCR (CD201), and ABCG2. Functionally, human CD157+ ECs isolated from muscle exhibited greater proliferative capacity than CD157− ECs. Cell-cell interaction analysis suggested active communication between CD157-positive ECs and surrounding cells, via the CXCL12-CXCR7 axis. Our findings identify a conserved gene signature for CD157+ ECs with potential relevance for vascular regeneration.