Humans cannot replace hair cells to restore their hearing but many animals, including zebrafish, can do so. Humans and zebrafish share more than 70% of their genes, which offers the potential for researchers to understand the biology of cell regeneration in zebrafish before translating the findings to humans.

A team from the National Human Genome Research Institute's Translational and Functional Genomics Branch used a combination of genomic techniques and computational-based machine learning to discover zebrafish hair cell regeneration relies on a network of transcription factors (Cell Genomics, September 14, 2022). They looked at the enhancer sequences within the zebrafish genome using single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin.

The study identified two families of transcription factors that work together to activate hair cell regeneration in zebrafish: Sox and Six transcription factors. The Sox transcription factors initiate the regeneration response in support cells and Six transcription factors cooperate to turn those support cells into hair cells.

Previous research identified some of the factors that convert support cells into hair cells, but what was not understood is how and where the genes encoding those factors turn on and are coordinated with other unknown factors. Now the combination of transcription factors has been pinpointed and further down the line, this group of zebrafish transcription factors could become a biological target that may lead to the development of novel therapy to treat hearing loss in humans, the researchers said.