New Studies Show Potential for Regenerating Hearing in Deafened Adults
Deafened adults who have lost their ability to hear may have hope for regaining it in the future, according to two new studies conducted by USC Stem Cell scientists. These groundbreaking studies, partially funded by the National Institutes of Health (NIH), offer valuable insights into why sensory hearing cells in the inner ear do not regenerate after damage and explore potential strategies to reverse this process.
The first study, led by John Duc Nguyen from USC Stem Cell laboratory, explains how certain genes responsible for the conversion of non-sensory supporting cells into sensory cells are naturally shut off through a process called epigenetic silencing. By understanding this mechanism, researchers hope to find ways to reactivate these genes and regenerate hearing. Nguyen, who is now working at biotech company Genentech, conducted his research under the guidance of Neil Segil, a renowned scientist who sadly passed away from pancreatic cancer in 2022.
The second study, headed by Emily Xizi Wang, also a former PhD student from the Segil Lab and currently working at Atara Biotherapeutics, focuses on the timing and mechanism by which progenitor cells in the inner ear gain the ability to form sensory hearing cells. The researchers identified two genes, Sox4 and Sox11, that play a crucial role in this process. These genes enhance the capacity of progenitor cells to respond to signals from the master regulator gene Atoh1, which triggers the formation of sensory hearing cells.
The findings of these studies have significant implications for the field of regenerative medicine. One of the key findings is the role of DNA methylation, a process that silences genes by attaching chemical compounds called methyl groups to DNA, making it inaccessible. The researchers discovered that an enzyme called TET can reverse this methylation process and restore the ability of supporting cells to convert into sensory hair cells. By blocking the activity of TET, the scientists observed that the supporting cells retained their DNA methylation and were unable to transform into sensory hair cells.
In an intriguing experiment, the researchers also found that gene silencing in supporting cells from chronically deafened mice was partially reversed, indicating that the loss of sensory hearing cells itself might trigger a natural reversal of gene silencing in supporting cells. This suggests that the supporting cells of chronically deaf individuals may already be primed to convert into sensory hearing cells.
The studies also shed light on the critical role of Sox4 and Sox11 genes in the development of sensory hearing cells. When these genes were absent in embryonic mice, the progenitor cells in the inner ear failed to develop into sensory hearing cells. Conversely, high levels of activity of these genes stimulated the formation of sensory hearing cells in both embryonic mice and mice with damaged sensory cells in the inner ear.
These groundbreaking studies not only contribute to scientific knowledge but also pay tribute to the late Neil Segil, who mentored and inspired a new generation of stem cell researchers. Gage Crump, a co-author on both papers and the interim chair of USC’s Department of Stem Cell Biology and Regenerative Medicine, highlights the lasting impact of Segil’s mentorship.
The findings of these studies open up a promising avenue for further research into the mechanisms that govern the differentiation of cells in the inner ear and the potential to promote the recovery of sensory hearing cells in adults. Scientists are hopeful that these discoveries will ultimately lead to new therapeutic approaches for treating hearing loss and restoring auditory function in deafened individuals.
The studies were supported by the National Institutes of Health and a consortium award from the Hearing Health Foundation. The researchers involved in these studies are committed to continuing their investigations to uncover more insights into the regenerative potential of hearing cells and advance the field of regenerative medicine.
In conclusion, these new studies provide exciting prospects for regenerating hearing in deafened adults. By understanding the mechanisms of gene silencing and the role of specific genes in the development of sensory hearing cells, researchers are one step closer to finding innovative solutions to address hearing loss. This research brings hope to millions of deaf individuals worldwide and paves the way for future breakthroughs in regenerative medicine.
