Transcriptomic Characterization of Dying Hair Cells in the Avian Cochlea

Abstract

Highlights: • New in vivo model to study cochlear hair cell death • Cochlear hair cells die rapidly and in synchronous fashion • Single cell RNA-seq reveals two stages of hair cell demise • Major types of dying cochlear hair cells express different sets of genes Summary: Sensory hair cells are prone to apoptosis caused by various drugs including aminoglycoside antibiotics. In mammals, this vulnerability results in permanent hearing loss because lost hair cells are not regenerated. Conversely, hair cells regenerate in birds, making the avian inner ear an exquisite model for studying ototoxicity and regeneration. Here we used single-cell RNAsequencing and trajectory analysis on control and dying hair cells after aminoglycoside treatment. Interestingly, the two major subtypes of avian cochlear hair cells, tall and short hair cells, responded differently. Dying short hair cells showed a noticeable transient upregulation of many more genes than tall hair cells. The most prominent gene group identified was associated with potassium ion conductances, suggesting distinct physiological differences. Moreover, the dynamic characterization of >15,000 genes expressed in tall and short avian hair cells during their apoptotic demise comprises a resource for further investigations towards mammalian hair cell protection and hair cell regeneration.