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

Area of Science:

• Vascular biology
• Auditory science
• Regenerative medicine

Background:

• Inner ear blood vessels, including the stria vascularis (SV) within the blood-labyrinth barrier (BLB), are crucial for hearing.
• The genetic and molecular makeup of cochlear vasculature remains largely unknown.

Purpose of the Study:

• To profile endothelial cells (ECs) and pericytes (PCs) in the adult mouse cochlea using single-cell RNA sequencing.
• To investigate the angiogenic potential and communication pathways within cochlear vasculature.
• To identify potential targets for vascular regeneration in the inner ear.

Main Methods:

• Single-cell RNA sequencing of mouse cochlear ECs and PCs.
• Ligand-receptor interaction analysis.
• Ex vivo explant models and dual fluorescent reporter mouse models.

Main Results:

• Cochlear ECs and PCs exhibit a distinct genetic signature with higher angiogenic potential than blood-brain barrier counterparts.
• Two PC subclasses were identified: Type 1 (high Acta2/Tagln) in pre-/post-capillary zones and Type 2 (low Tagln, high Kcnj8/Abcc9) in capillaries.
• PCs demonstrated tip-like behavior in vitro, and dual reporter models showed PCs can transition into tip cells (NG2/PECAM-1+).
• Active EC-PC communication via adhesive signals, gap junctions, and vesicle trafficking was observed.

Conclusions:

• The study defines the molecular profile of cochlear blood vessels.
• Pericytes are identified as key players with regenerative potential, capable of transitioning into tip cells.
• Targeting pericytes could facilitate vascular regeneration, potentially aiding hearing restoration in cases of compromised cochlear blood flow.