The quality of life can be greatly impacted by age-related hearing loss. Adults who have lost their hearing are unable to regain it because damaged sensory hair cells in the inner ear do not grow back.
By converting nearby supporting cells into new hair cells, it may be possible to renew the mechanosensory hair cells that are responsible for sensing sound. In August 2023, the scientific community witnessed a significant leap forward in the quest for hearing regeneration. Two groundbreaking studies, unveiled unprecedented insights into the intricate mechanisms underlying hearing loss and regeneration. These studies, led by dedicated researchers:
- John Duc Nguyen, Ph.D., the first paper author. Neil Segil’s USC Stem Cell lab is where Nguyen received his doctorate.
- Emily Xizi Wang, Ph.D., the second paper author. She also conducted her research as a doctoral student in the Segil Lab.
University of Southern California (USC) stem cell researchers explain why this is the case and how we might be able to change it in two new studies that were published in the Proceedings of the National Academy of Sciences (PNAS) and supported in part by the National Institutes of Health and Hearing Health Foundation.
Study 1: DNA Methylation and Hair Cell Regeneration
The first study, led by Dr. John Duc Nguyen and his team, delves into the profound impact of DNA methylation on the regeneration of mechanosensory hair cells in the cochlea—a critical component of the inner ear responsible for sound detection. Age-related hearing loss has long been a concern, primarily because the ability of supporting cells to transdifferentiate into new hair cells diminishes with age. This study revealed that supporting cells accumulate DNA methylation, an epigenetic mechanism that silences genes, thereby preventing the reactivation of the hair cell gene program needed for transdifferentiation.
Intriguingly, the study found that blocking the activity of the ten-eleven translocation (TET) enzyme extends the window in which transdifferentiation can occur. Furthermore, the loss of hair cells due to deafening partially reverses DNA methylation in supporting cells, offering a potential therapeutic target for hearing regeneration. These findings are a beacon of hope for individuals suffering from hearing loss, as they open doors to innovative treatments and interventions.
“In the non-sensory supporting cells of the inner ear, key genes required for conversion to sensory cells are shut off through a process known as ‘epigenetic silencing.’ By studying how the genes are shut off, we begin to understand how we might turn them back on to regenerate hearing,” says John Duc Nguyen, Ph.D.
Study 2: SoxC Transcription Factors and Competence for Sensory Differentiation
In the second groundbreaking study, Dr. Emily Xizi Wang and her team explored the role of SoxC transcription factors (Sox4 and Sox11) in shaping the epigenetic landscape necessary for sensory differentiation in the mammalian organ of Corti. This structure, found in the inner ear, is vital for hearing as it contains both mechanosensory hair cells and supporting cells.
The research revealed that SoxC factors play a pivotal role in establishing a permissive chromatin landscape, enabling the activation of the hair cell gene regulatory network upon differentiation cues. This newfound understanding of competence acquisition in the lineage-specific progenitor cells within the organ of Corti has far-reaching implications. It not only advances our knowledge of tissue development and regeneration but also paves the way for innovative therapeutic strategies targeting the epigenetic regulation of sensory differentiation.
“We focused on the genes Sox4 and Sox11 because we found that they are necessary for forming sensory hearing [hair] cells during development,” says Emily Xizi Wang, Ph.D.
Conclusion
The two studies unveiled in August 2023 represent a momentous step forward in the field of hearing regeneration. They shed light on the intricate molecular mechanisms underlying hearing loss and offer promising avenues for the development of treatments and interventions. As we look to the future, these studies provide renewed hope for those affected by hearing impairment, emphasizing the importance of continued investment in scientific research and innovation. Through the collaborative efforts of dedicated researchers and the support of organizations like the National Institutes of Health and the Hearing Health Foundation, we inch closer to a world where hearing loss is not a permanent condition but a challenge that can be overcome.
About Dr Zhanneta Shapiro
Dr Zhanneta Shapiro received her Masters of Science from Brooklyn College in 2005 and completed her Doctorate of Audiology from Florida University in May 2008. Her graduate training was in various hospitals in the tri-state area and a residency period completed at Ear Nose and Throat Associates of New York. [ Learn More ]
