Dynamic cellular composition and immune landscape revealed by single-cell transcriptome profiling in a brain arteriovenous malformation.

Background: Cerebral arteriovenous malformation is a congenital blood vessel abnormality with its immune mechanism remains unclear. Our study characterized the change of cellular composition and gene expression landscape in brain arteriovenous malformation (bAVM).

Methods: We conducted single-cell RNA sequencing analysis on one bAVM sample and three healthy control (HC) samples. Cell clustering analysis and cell type annotation were used to identify the major cell types in bAVM and HC samples. Critical differentially expressed genes between bAVM and HC sample were analyzed in each cell types to explore the functional changes of each kind of cells. We also examined the cell communication change in bAVM sample and identified the significantly changed cellular interaction pathways.

Results: 5 major cell types were identified including NK cells, monocytes, fibroblasts, endothelial cells (EC), tissue stem cells and smooth muscle cells (SMC). In bAVM sample, proportion of monocytes raised significantly while SMC decreased. Inflammation and cell migration related genes expression and cell communication pathways changed dramatically in bAVM sample.

Conclusion: Inhibition of monocyte-endothelium interaction and promotion of NK cells interaction were found in bAVM sample, which may reveal a new mechanism about inflammation response and cellular impairment in the disease progression.