Researchers at the National Institutes of Health (NIH) discovered a unique network of proteins that restores hearing in zebrafish through cell regeneration. In collaboration with the team at the National Human Genome Research Institute (NHGRI), who led the study, they discussed in the study how the findings could open new doors for developing treatments for hearing loss in humans.
In the study titled "A Regulatory Network of Sox and Six Transcription Factors Initiate a Cell Fate Transformation During Hearing Regeneration in Adult Zebrafish" published in Cell Genomics, researchers used zebrafish inner ears as a model for sensorineural regeneration and deep learning to monitor hair cell regeneration patterns.
Zebrafish Can Regenerate Lost Hair Cells
Approximately 15% of American adults, or 37.5 million people in the US, experience some form of hearing problems, wherein most cases come from the loss of hearing receptors or hair cells in the inner ear. Hair cells move and bend to sound waves that travel in the ear and send signals to the brain to process the sound.
Humans and zebrafish share more than 70% of their genes, which offers the potential to understand the biology of cell regeneration. But unlike humans, zebrafish can replace damaged or lost hair cells after an injury through regeneration. According to Phys.org, researchers studied zebrafish to understand the fundamental properties of regeneration.
Shawn M. Burgess, Ph.D., the senior investigator in the NHGRI Translational and Functional Genomics Branch, explained that humans and other mammals are born with a set of hair cells that are slowly lost through aging and trauma. But zebrafish can regenerate hair cells and recover from hearing loss. This ability has remained a mystery that scientists try to unravel in their studies.
A zebrafish, which shares a similar genetic structure to humans, is seen in a fish bowl during a press conference by Kelvin Leung at the Baptist University in Hong Kong on October 4, 2018.
The Role of Regulatory Network of Proteins in Cell Regeneration in Zebrafish
Using genomic techniques and computational-based machine learning, researchers found that zebrafish rely on a unique network of proteins known as transcription factors. The team first looked at the enhancer sequences within the zebrafish genome to identify transcription factors, which are considered to be keys that turn off or on specific genes.
Then they used single-cell RNA sequencing and a single-cell array to identify the enhancer sequences and corresponding transcription facts responsible for cell regeneration in zebrafish.
Erin Jimenez, Ph.D., a postdoctoral fellow in the Burgess laboratory, said they identified two families of transcription factors called Sox and Six transcription factors. These two work together to activate cell regeneration in zebrafish.
The Sox transcription factors trigger regeneration response in support cells. Then both Sox and Six transcription factors turn support cells into hair cells. According to The Well News, support cells start replicating when hair cells in zebrafish die. They are like stem cells because they can become any other cell type.
Previous studies have shown some factors that convert support cells into hair cells. Until this study, none explain how and where encoding those factors are. Jimenez believes that the two families of transcription factors identified in this study could lead to future developments in treatment for hearing loss in humans.
RELATED ARTICLE: Deafness Cure: Scientists Identified 'Master Gene' That Could Regrow Lost Ear Hair Cell Involved in Hearing Loss
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