Vascular control of tumor immunity in the central nervous system
Aging is a major risk factor of cardiovascular disease and leads to the decline in cardiac diastolic and systolic functions, while augmenting fibrosis and hypertrophy. However, the impact of aging on endothelial cell (EC) intrinsic and paracrine effects are not well understood. In this project, we will continue to explore the impact of aging on the endothelial transcriptome and chromatin remodeling by using single-nucleus RNA and ATAC sequencing, respectively. First analyses revealed an age-dependent transcriptional dysregulation of the vascular endothelial growth factor Vegfb and an epigenetic regulation of the transcription factor Zbtb16. We will hence address how Vegfb affects cardiac aging and moreover assess the intrinsic effect of the epigenetically regulated transcription factor Zbtb16 in EC. We will further use spatial transcriptomics to identify transcriptional signature and potential paracrine activities of senescent cells in the aging heart.