By Stefan Heller, Ph.D.
A major goal of the work conducted by Hearing Health Foundation’s Hearing Restoration Project (HRP) in recent years has been to obtain a complete set of genes that are active in each cell type in the chicken inner ear. In 2021 my laboratory provided an inventory of all genes expressed in the chicken hearing organ, also known as the basilar papilla.
Now, one year later, we have inventoried the genes expressed in the chicken utricle, an important balance organ. As detailed in our study published in the journal Cell Reports in September 2022, we identified genes that define three different sensory hair cell types and two distinct supporting cell groups.
The figure shows the different groups of cells in the typical chicken utricle. Supporting cells consist of two groups (S1 and S2). Activated supporting cells that will divide are identified in group S3. These cells divide and generate a new S3 cell and a new hair cell. Newly generated hair cells are clustered in group S6 and will, over time, mature into one of the three different hair cell types of the utricle (S5–S8). Credit: Scheibinger et al./Cell Reports
The avian utricle, in contrast to the basilar papilla, continuously produces new hair cells throughout the animal’s life. Our team identified the sequence of gene expression changes in supporting cells during this natural process of new hair cell production. This knowledge will become important in future comparative studies where the HRP consortium plans to compare the repertoire of genes active during hair cell regeneration in chicken and zebrafish with existing gene expression in the mouse and human inner ear.
Hair cell regeneration does not naturally happen in mice and humans, and therefore, it will be important to identify the genes that are missing in supporting cells from these species. This knowledge, in turn, will guide the selection of candidate genes for potential future therapeutic approaches.
This paper concludes a string of three publications by our lab in 2021 and 2022 that establish a baseline for investigating the molecular mechanisms of auditory hair cell regeneration in chickens. Although still a work in progress, our team will present multiple abstracts at the February 2023 Association for Research in Otolaryngology meeting in Orlando, where we will discuss novel findings about the molecular pathways that initiate auditory hair cell regeneration in birds.
This is an exciting time for us and the HRP consortium because it demonstrates that the long-term investment into a systematic research approach with different animal models was worthwhile. We have now identified the first events that lead to proliferative hair cell regeneration in birds, which provides new leads that can be translated to mice and ultimately to humans.
The ability to monitor 20,000 genes in parallel in every individual cell in the regenerating inner ear is extremely powerful. Still, it also provides an incredible challenge to identify the significant genes that ultimately can be targeted with a drug-based approach. We are off to a promising start, and we tackle this large puzzle with an incredibly motivated team. We are thankful for the support from Hearing Health Foundation that enables this work.
Hearing Restoration Project member Stefan Heller, Ph.D., is a professor of otolaryngology–head & neck surgery at Stanford University. He is also a 2001–2002 Emerging Research Grants scientist. For more, see hhf.org/hrp.
Applications are now open for the 2023-2024 Emerging Research Grants cycle. See hhf.org/how-to-apply for more information.
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Their experiments revealed a class of DNA control elements known as “enhancers” that, after injury, amplify the production of a protein called ATOH1, which in turn induces a suite of genes required to make sensory cells of the inner ear.