Researchers at the Del Monte Institute of Neuroscience are studying possible mechanisms involved in the regeneration of hair cells in the mammalian ear. In January 2023, they published a study in the journal ‘Frontiers of Cellular neuroscience’ describing the role of a gene called ERBB2 in activating the growth of new hair cells in neonatal mice.
Hearing Loss
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Can adult mammals regenerate their hair cells?
It is impossible to restore hearing loss yet because of the death of hair cells in the cochlea of adult mammals. The hair cells are integral in the hearing process, and their loss results in permanent hearing loss. In birds, the regenerative potential in hair cells exists and manifests due to the growth of supporting cells and the formation of new hair cells. This process leads to the restoration of hearing. The regenerative potential in cochlear hair cells has also been observed in young mammals. However, the current understanding is that as mammals grow, the hair cells lose the ability to regrow after injury.
Why was this study needed?
Through previous research, scientists know about the role of the growth gene ERBB2 in activating the development of new hair cells. However, the underlying mechanisms involved in this activation process are unclear. In this study, scientists sought to understand the mechanism of this activation process by studying the ERBB2 signaling pathway in young mice.
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How did the scientists study the ERBB2 signaling pathway?
Using single-cell RNA sequencing, they compared cells with ERBB2 over-signaling with a control set of cells in which no such signaling mechanism was involved. They observed that ERBB2 was involved in the activation of stem cell-like developments. This activation occurred through the up-regulation of the expression of multiple proteins of which SPP1 is the most up-regulated protein. Mmp9, Timp1, and Dmp1 are the other significantly upregulated proteins in this pathway.
Activation of these proteins leads to a series of cellular events resulting in the binding of SPP1 to the CD44 receptor. The CD44 receptor activation leads to the proliferation of supporting cells which leads to the presence of hair cells in the cochlea. According to researchers, these findings demonstrate the regenerative potential of the cochlea.
Is the regeneration in hair cells limited to young mice?
Scientists also checked this process in adult mice cells and found that this proliferative process also exists in adult mice cells. They believe it corroborates that regenerative capacities are not limited to young mice but are also present in adult mice.
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How do microenvironmental changes affect the potential for regeneration?
Previously, it has been proposed that adult mammalian cochlear epithelium loses its flexibility which is the underlying mechanism for losing regenerative capacity. Scientists mention that their results show that this ERBB2 signaling pathway induces changes in the extra-cellular matrix that would enhance flexibility in the organ of Corti in the cochlea of the mammalian ear. They predict this would allow increased movement of cells, creating optimum microenvironmental conditions for regeneration.
Scientists hope to continue their investigation to understand if these pathways can improve auditory function after damage in adult mammals.
Significance
Hearing loss is a significant public health issue in the US. Around 13 percent of the population has hearing loss in both ears, and sensorineural hearing loss (the one due to damage to hair cells) makes up around 90% of those people. Scientists have been studying ways to regenerate hair cells and restore hearing for many years. The complexities of it lay in specific microenvironmental requirements for hair cells to exhibit their regenerative potential.
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The current study explains the role of the ERBB2 growth gene in regenerating hair cells. If the studied mechanism exhibits similar results about regenerating damaged hair cells in humans, it may hint towards finding possible solutions for restoring hearing loss. However, the study provides a direction about the underlying mechanisms involved in regeneration and outlines different steps in this process. It also provides insights about specific changes that are required for this process to occur.
Detailed information about the authors, participating institutions, funding, and study methods are available at the provided link.
References
Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor indicates a cell-specific response that promotes CD44 activation (Accessed March 22, 2023)
Can hearing loss be reversed? Research reveals clues that could regrow the cells that help us hear (Accessed March 22, 2023)
