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

Area of Science:

• Vascular Biology
• Auditory Science
• Regenerative Medicine

Background:

• Inner ear blood vessel integrity, particularly the stria vascularis (SV) microvasculature within the blood-labyrinth barrier (BLB), is critical for hearing.
• The genetic and molecular makeup of cochlear vasculature remains largely uncharacterized, hindering therapeutic development.

Purpose of the Study:

• To define the molecular signature of cochlear endothelial cells (ECs) and pericytes (PCs) using single-cell RNA sequencing.
• To investigate the heterogeneity and functional characteristics of cochlear pericytes.
• To explore EC-PC communication and pericyte plasticity in the cochlea.

Main Methods:

• Single-cell RNA sequencing of adult mouse cochlear ECs and PCs.
• Ex vivo explant model for observing vascular sprouting.
• Ligand-receptor interaction analysis.
• Dual fluorescent reporter mouse models to track pericyte behavior.

Main Results:

• Cochlear vasculature exhibits a distinct genetic profile and higher angiogenic potential compared to the blood-brain barrier (BBB).
• Two pericyte subclasses were identified: Type 1 (high Acta2, Tagln) in pre-/post-capillary zones and Type 2 (low Tagln, high Kcnj8/Abcc9) in capillaries.
• Both pericyte subclasses demonstrated tip-like behavior in vitro, and PCs showed phenotypic plasticity, adopting tip-associated states during vascular sprouting.
• Active EC-PC communication via adhesive signals, gap junctions, and vesicle trafficking was confirmed.

Conclusions:

• This study provides a comprehensive molecular definition of cochlear vascular cells.
• Pericytes are identified as key players with potential for vascular regeneration in the inner ear.
• Targeting pericytes may offer novel therapeutic strategies for hearing restoration in cases of compromised cochlear blood flow.