PROJECT SUMMARY (Description) Perivascular fibroblasts (PVFs) and vascular endothelium are important responders to hypertension and cerebral ischemia. Long-term aberrant interactions of PVFs and endothelium may also promote vascular cognitive disorders (VCD), but the mechanisms remain poorly understood. This project will use PVF-specific single-cell RNA-Seq and vascular endothelium-specific or TRAP-Seq to test the impacts of hypertension and cerebral ischemia on gene expression. Outcomes of this project may suggest novel therapeutic targets. Aim 1 will test the transcriptome changes of endothelial cells in a mouse model of chronic hypertension (ReninTg) with and without partial cerebral ischemia. Aim 2 will use bitransgenic ReninTg and Pdgfra-H2BGFP mice, with and without partial cerebral ischemia, to isolate PVFs for single-cell RNA-Seq comparison. In summary, this project will use open-ended genomic methods to correlate, for the first time, the transcriptome adaptations by PVFs and vascular endothelium to hypertension and combined hypertension/ischemia.