Transcriptomic characters of cochlear vascular cells with pericyte-driven angiogenetic activity

The normal structure and function of inner-ear blood vessels, including the microvascular network of the stria vascularis (SV) within the blood-labyrinth barrier (BLB), are essential for auditory function. Despite this, the genetic and molecular characteristics of cochlear vasculature are largely unexplored. In this study, we used single-cell RNA sequencing to profile endothelial cells (ECs) and pericytes (PCs) from the adult mouse cochlea. We found a distinct genetic profile and a higher angiogenic potential than observed in the blood-brain barrier (BBB). Two subclasses of PCs were identified. Type 1 PCs, with high levels of α-smooth muscle actin (Acta2) and Tagln, are located on pre-/post-capillary zones. Type 2 PCs, characterized by low Tagln and high Kcnj8/Abcc9 levels, are found specifically in capillary regions. In an ex vivo explant model, both subclasses showed tip-like behavior during sprouting. Ligand-receptor analysis indicated active EC-PC communication. This communication is mediated by adhesive signals, gap junctions, and vesicle trafficking. Using dual fluorescent reporter mouse models, we showed for the first time that PCs can exhibit tip-associated phenotypic plasticity with detectable NG2/PECAM-1 overlap at the sprout front. This tip-associated state may occur from existing cells or progenitors within the vascular niche. Our findings define the molecular signature of cochlear vessels and identify PCs as targets to promote vascular regeneration. This could have implications for hearing restoration when cochlear blood flow is compromised.