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Updated: Nov 11, 2025
In Ovo and Ex Ovo Methods to Study Avian Inner Ear Development
Published on: June 16, 2022
Transcriptomic characterization of dying hair cells in the avian cochlea
Nesrine Benkafadar1, Amanda Janesick1, Mirko Scheibinger1
1Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Abstract:
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 use single-cell RNA sequencing 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, respond differently. Dying short hair cells show a noticeable transient upregulation of many more genes than tall hair cells. The most prominent gene group identified is 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 toward mammalian hair cell protection and hair cell regeneration.
Insights
Avian hair cells regenerate after drug-induced damage, unlike in mammals. Dying short hair cells show greater gene changes, particularly in potassium channels, offering insights into hearing loss and regeneration.
Area of Science:
- Ototoxicity and Regenerative Biology
- Cellular Biology
- Genomics
Background:
- Sensory hair cells are vital for hearing and are susceptible to apoptosis from drugs like aminoglycosides.
- Mammalian hair cell loss is permanent, leading to irreversible hearing loss, whereas avian hair cells can regenerate.
Purpose of the Study:
- To investigate the differential responses of avian cochlear hair cell subtypes to aminoglycoside-induced apoptosis.
- To identify key genes and pathways involved in hair cell death and regeneration.
Main Methods:
- Single-cell RNA sequencing was performed on control and aminoglycoside-treated avian cochlear hair cells.
- Trajectory analysis was used to characterize gene expression dynamics during apoptosis.
- Comparative analysis of gene expression between tall and short hair cell subtypes.
Main Results:
- Avian cochlear hair cells, specifically short hair cells, exhibit a transient upregulation of numerous genes during apoptosis, more so than tall hair cells.
- A prominent group of upregulated genes in dying short hair cells is associated with potassium ion conductances, indicating distinct physiological properties.
- Dynamic characterization of over 15,000 genes in both hair cell subtypes during apoptotic demise.
Conclusions:
- Avian hair cell subtypes display differential responses to ototoxic drugs, with short hair cells showing a more pronounced gene expression response.
- The identified gene expression patterns, particularly those related to potassium channels, provide a valuable resource for understanding hair cell vulnerability and regeneration.
- This study offers a foundation for developing strategies to protect mammalian hair cells and promote regeneration, potentially restoring hearing function.
Related Concept Videos
01:22Hair Cells
01:13The Cochlea