A study of USC Stem Cellpublished in the magazine ‘Proceedings of the National Academy of Sciences‘ (PNAS), has identified key genetic regulators that allow certain animals, such as fish and lizards, to regenerate their hearing capacity naturally. This discovery could be a crucial advance in developing treatments that stimulate cell regeneration. auditory sensory cells in patients with hearing loss and balance disorders.
These findings also open the door to new therapies that could reverse deafness and improve the quality of life of millions of people affected by these health problems.
The study, led by Tuo Shi of the Keck School of Medicine at University of Southern California (USC), has focused on two types of cells present in the inner ear: the cells sensorywhich are responsible for detecting sound, and the brain cells mediumwhich create a suitable environment for the functioning of sensory cells.
In animals with a high capacity for regeneration, such as fish and lizards, supporting cells have the ability to transform into new sensory cells after injury, a process that does not occur in humans or other mammals, such as mice. This phenomenon has caught the attention of scientists, who decided to investigate how this regenerative process is activated in these species and if it is possible to apply it to humans.
The team of researchers studied how the genome folds in the sensory and supporting cells of the inner ear of Zebra fish and green anole lizards. They compared DNA control elements related to sensory genes in these species with those in mice, which cannot regenerate sensory cells after injury. They discovered boostersDNA control elements that amplify the production of the ATOH1 protein, key to forming new sensory cells. Using CRISPR, they removed five enhancers in zebrafish, which blocked both the development and regeneration of these cells, highlighting their essential role.
“In the past, removing individual enhancers did not usually have a big impact, but by removing these five enhancers in zebrafish, we discovered their crucial role in both development and regeneration,” he explains. Gage Crump professor in the Department of Stem Cell Biology and Regenerative Medicine at USC.
The results showed that although zebrafish also possess sensory cells in a specialized aquatic organ called the lateral line, which detects water flow and pressure, the genetic deletions only affected the cells in their inner ears.
Reverse deafness
Furthermore, they found that mice also possess equivalent enhancers, which are active during embryonic development in the progenitor cells that give rise to both sensory and support cells in the inner ear. However, unlike regenerative species such as fish and lizards, mice do not maintain these enhancers in an open configuration in their supporting cells throughout adulthood, preventing them from replacing damaged sensory cells.
“What we have found is that, in regenerative vertebrates, sister cell types keep these enhancers open from development through adult stages, allowing them to replace each other after injury,” explains Crump.
In the future, he adds, “strategies aimed at opening these enhancers in the human inner ear could be used to enhance our regenerative abilities natural and reverse deafness.
The findings open new possibilities for the treatment of hearing loss, suggesting that it is possible to reactivate genetic mechanisms in humans that could allow the regeneration of sensory cells in the inner ear, similar to what occurs in regenerative species such as fish. and the lizards.
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