A groundbreaking study from USC Stem Cell, published in the Proceedings of the National Academy of Sciences (PNAS), has shed light on crucial gene regulators that enable some deafened animals, like fish and lizards, to restore their hearing naturally.
These discoveries may open new avenues for innovative strategies to promote the regeneration of sensory hearing cells in people suffering from hearing loss or balance disturbances.
Research Overview
Led by Tuo Shi, with valuable contributions from Ksenia Gnedeva and Gage Crump at the Keck School of Medicine, the research delves into two key types of cells located in the inner ear: sensory cells, which are tasked with detecting sound, and supporting cells, which ensure the optimal environment for the sensory cells to function.
Remarkably, in species known for their regenerative prowess, such as fish and lizards, the supporting cells can transform into new sensory cells following injury.
Unfortunately, this remarkable capability is absent in mammals, including humans and mice.
Gene Regulation Insights
To harness a better understanding of this regeneration phenomenon, the researchers focused on how genes, usually confined to sensory cells, can be reactivated in the supporting cells of these extraordinary animals.
They carried out a comparative study of DNA regulatory elements tied to sensory genes in zebrafish and green anole lizards, contrasting these results with those from mice that are unable to regenerate sensory hearing cells after damage.
The research revealed fundamental insights into what allows certain vertebrates to replace lost sensory cells and restore hearing.
By examining regenerative species like zebrafish and lizards against non-regenerative ones such as mice, the team identified crucial DNA regulatory elements known as “enhancers.” These enhancers significantly increase the production of a protein called ATOH1 after an injury, which in turn activates a suite of genes essential for developing inner ear sensory cells.
Implications for Human Health
In a fascinating twist, the scientists employed the CRISPR gene-editing technique to disrupt five of these enhancers in zebrafish.
This manipulation led to serious repercussions for both the formation of sensory hearing cells and their ability to regenerate post-injury—a stark difference from previous experiments where individually deleting enhancers had minimal impacts.
Intriguingly, the researchers found that while mice have similar enhancers, they remain active only during developmental stages in progenitor cells that eventually differentiate into sensory and supporting cells in the inner ear.
In contrast, only regenerative species like fish and lizards keep these enhancers in an accessible state in their supporting cells throughout their lives, allowing for the production of new sensory cells when needed.
The findings indicate that regeneration-capable vertebrates maintain open enhancers from their developmental periods into adulthood.
This adaptation facilitates the reciprocal replacement of damaged cells.
The researchers propose that future efforts aimed at activating these enhancers in the human inner ear could boost our natural regenerative capacity, potentially leading to new solutions for deafness.
Source: ScienceDaily