Santa Maria, P. | Search bioRxiv

bioRxiv2026

Proteomic Remodeling of the Cochlea During Chronic Suppurative Otitis Media Reveals Immune-Driven Injury Pathways

Chronic suppurative otitis media (CSOM) is a persistent middle ear infection in which chronic inflammation drives irreversible sensorineural hearing loss (SNHL), yet the molecular mechanisms linking middle ear chronic infection to cochlear injury remain poorly defined. Using a murine model of CSOM induced by Pseudomonas aeruginosa (PA) persisters, a quantitative proteomic profiling of cochlear tissue was performed at seven days post-infection. Mass spectrometry revealed over 250 proteins that were significantly altered, indicating broad immune activation, oxidative stress, and disruption of ion homeostasis. Among the top candidates, HSPA5, MPO, and ATP2A2 were strongly associated with inflammatory stress and cellular injury pathways. These findings identify immunometabolic remodeling and macrophage-driven inflammation as central mechanisms linking chronic middle ear infection to cochlear injury.

immunology↗

bioRxiv2022

Single-cell transcriptomic atlas reveals increased regeneration in diseased human inner ears

Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe previously unknown markers of 25 sensory and non-sensory cell types, with genes of hair cell and supporting cell subtypes displaying striking divergence between mice and humans. We further uncovered transcriptomes unique to hair cell precursors, which we validated to be 14-fold more robust in vestibular schwannoma utricles, representing ongoing regeneration in humans. Lastly, trajectory analysis of the supporting cell-hair cell axis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including mTOR signaling and synaptogenesis. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ears and tools to stimulate human inner ear regeneration.

cell biology↗