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

## TL;DR

This study explores the genetic and molecular features of blood vessels in the mouse cochlea, revealing unique properties of pericytes that could aid in hearing restoration.

## Contribution

The study identifies two subclasses of pericytes in cochlear vessels and shows their angiogenic potential and communication with endothelial cells.

## Key findings

- Two subclasses of pericytes were identified with distinct gene expression profiles and locations in the cochlear vasculature.
- Pericytes can transition into tip cells during sprouting, as demonstrated using dual fluorescent reporter mouse models.
- Ligand-receptor analysis revealed active communication between endothelial cells and pericytes via adhesive signals and vesicle trafficking.

## Abstract

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 transition into tip cells by co-expressing NG2/PECAM-1 signals. This transition 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.