Angiodiversity—A tale retold by comparative transcriptomics

Endothelial cells (ECs) that line all the blood vessels of the cardiovascular system display incredible functional and structural heterogeneity, both spatially across different organs and tissues, as well as temporally during growth and differentiation. This heterogeneity has been termed “angiodiversity,” (Koch et al., 2021) and neither its origins nor its maintenance are well understood. Before the 1960s, the endothelium was thought to be largely homogeneous. However, discovery of organ-specific differences in EC substructures and gene expression sparked wide interest in better understanding the regionalization of blood vessels. These local vascular differences evoked the idea of an “angiogenic zip code.” (Folkman, 1999) This newly recognized EC regionality stimulated the imagination, as it offered a possible avenue for the development of targeted therapeutics that can be tailored to specific tissue needs. Here, we examine the vast array of different vascular beds, with a focus on the brain and kidney, and we discuss the numerous transcriptomic studies that work to describe them. Together, these new “omics” studies of blood vessels are identifying tissue-specific endothelial molecular signatures, thereby establishing a useful spatiotemporal “vasculome.”