Pharmacologically reversible zonation-dependent endothelial cell transcriptomic changes with neurodegenerative disease associations in the aged brain

Profiling EC transcriptomic changes in the aged mouse brain

To obtain ageing-associated genome-wide expression changes of neurovascular cells, we performed high-throughput scRNA-seq of brain vascular cells from young adult (2–3 months old) and aged (18–20 months old) C57BL/6J mice (n = 5 mice for each group) (Fig. 1a). After quality control filtering (see Methods section), we obtained a total of 43,922 single-cell transcriptomes. These included 31,555 cells from young adult and 12,367 cells from aged mouse brains (Fig. 1a), among which there were 12,357 brain ECs, 1425 smooth muscle cells (SMC), 642 pericytes (PC), 9642 astrocytes (AC), and 11,767 microglia (MG), alongside numerous other major brain cell type clusters (Fig. 1b and Supplementary Fig. 1a). The ECs had high expression of known EC-specific marker genes (e.g. Cldn5, Flt1, Pecam1, and Cdh5) and did not express…