New genetic tools for central and peripheral vascular endothelia.

The divergence between the central and peripheral vascular system, particularly the emergence of the blood-brain barrier (BBB), is central to the brain's homeostasis and functions. However, the molecular and genetic constituents that separating the BBB vascular cells from the rest remain elusive. Using single cell transcriptomics, we identified new cerebrovascular markers, e.g. zinc finger protein Zic3 is explicitly found in adult brain endothelial cells and the Atp13a5 ATPase is only expressed in brain pericytes. Using new genetic models, we further confirmed the specificity of Zic3 in cerebrovasculature. Additionally, we developed a mouse model based on Plvap , and confirmed it is specific for endothelial cells of the peripheral tissue and circumventricular organs in brain. In-depth transcriptomics analysis between Zic3 (+) and Plvap (+) endothelial cells revealed that genetic programs associated with lipid metabolism, transporter systems and tight junction signaling are critical drivers behind the separation of central and peripheral endothelia. These new murine genetic tools will further aid our understanding of vascular heterogeneity and BBB specialization.