A Cell Type–Specific Approach to Detail the Role of a Small Molecule in Hair Cells

Genetic variants in a small molecule called microRNA-96 (miR-96), which is present in the hair cells of the inner ear, lead to progressive hearing loss in both mice and humans.

In a study published in Frontiers in Audiology and Otology in May 2024, Ronna Hertzano, M.D., Ph.D., and team present the first dataset of gene expression profiles specifically from the hair cells of newborn mice with variant miR-96. They examined mice with three different levels of miR-96: typical miR-96 levels, one variant copy of miR-96, and two variant copies of miR-96.

Genes that are more active in miR-96–variant hair cells are also found more in the supporting cells of wildtype (typical) mice than in their hair cells. This heatmap shows the activity levels of these genes in a dataset of wildtype newborn mice. Credit: Gwilliam et al./Frontiers in Audiology and Otology

The team performed a technique called RNA-sequencing on the hair cells from newborn mice in these three groups. They then compared the gene expression levels between the mice with two variant copies of miR-96 and the typical mice to identify genes that were turned up or down.

The researchers found 215 genes that were more active (upregulated) and 428 genes that were less active (downregulated) in the hair cells of the mice with two variant copies of miR-96 compared with the typical mice. 

Many of the genes that were less active in the hair cells of the mice with two variant copies of miR-96 are known to be important for the proper development of hair cells and hearing ability. When these genes—Myo15a, Myo7a, Ush1c, Gfi1, and Ptprq—don't work correctly, it can lead to deafness. 

These genes are involved in biological processes and functions related to how the hair cells sense and transmit sound information from the inner ear to the brain. Having lower levels of these genes likely disrupts the hair cells' ability to perform their sound detection role properly.

Interestingly, some of the genes that were more active in the variant hair cells are typically more active in the supporting cells than in the hair cells. It could be that when miR-96 is a variant, some genes more specific to supporting cells—and which are typically kept turned off in hair cells—incorrectly become activated in the hair cells. 

The paper supports that miR-96 plays an important role in the proper development of hair cells, possibly by suppressing the activity of genes that are typically more active in supporting cells. The dataset this study generated is now publicly available for further research through the gEAR portal (umgear.org/p?l=miR96).

This is adapted from the paper in Frontiers in Audiology and Otology. Ronna Hertzano, M.D., Ph.D., is the head of the Neurotology Branch in the Division of Intramural Research at the National Institute on Deafness and Other Communication Disorders. She is a 2009–2010 Emerging Research Grants scientist and a member of HHF’s Hearing Restoration Project.


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