Confocal picture of grownup zebrafish hair cells (inexperienced) within the auditory organ of the interior ear. Credit score: Erin Jimenez, Ph.D.
A research demonstrates how transcription components assist cell regeneration.
Researchers on the National Institutes of Health have recognized a specific protein community that’s crucial for cell regeneration to revive listening to in zebrafish. Researchers on the Nationwide Human Genome Analysis Institute (NHGRI) led the analysis, which can assist in the creation of human listening to loss remedies. The findings have been lately revealed within the journal Cell Genomics.
Many animals, like zebrafish, might recuperate their listening to after harm via the regeneration of hair cells, nevertheless, human hair cell loss can’t be restored. The regenerating properties of zebrafish hair cells impressed researchers to make use of this species to higher perceive sure basic properties of regeneration.
About 37.5 million Individuals undergo from listening to loss, and the vast majority of these situations are attributable to the lack of listening to receptors known as “hair cells” within the interior ear. When sound enters our ears, bristles that protrude from these tiny hair cells transfer and bend, inflicting electrical indicators to be despatched via nerves and into our brains that permit us to course of sound.
Regardless of having fairly distinct appearances, people and zebrafish have greater than 70% of the identical genes on the genomic stage. This genomic similarity permits researchers to higher perceive the biology of cell regeneration in zebrafish earlier than translating their outcomes to people.
Brightfield picture of a two-day-old zebrafish embryo. Credit score: Erin Jimenez, Ph.D.
Erin Jimenez, Ph.D., a postdoctoral fellow within the laboratory of Shawn Burgess, Ph.D., senior investigator within the Nationwide Human Genome Analysis Institute’s (NHGRI) Translational and Purposeful Genomics Department, led the research in collaboration with researchers Ivan Ovcharenko, Ph.D., and Wei Tune, Ph.D., on the Nationwide Library of Medication’s Nationwide Heart for Biotechnology Data.
“People and different mammals are born with a set variety of hair cells which might be slowly misplaced via growing old and trauma. Nonetheless some animals, comparable to zebrafish, can regenerate hair cells and recuperate listening to after harm,” mentioned Burgess. “How and why regeneration occurs in these animals stays a thriller that many scientists wish to unravel.”
Utilizing a mix of genomic methods and computational-based machine studying, Jimenez and her collaborators discovered that hair cell regeneration in zebrafish relied on a community of proteins that may swap genes on and off, referred to as transcription components. To correctly establish which transcription components have been at play, the researchers first had to have a look at the enhancer sequences inside the zebrafish genome.
If transcription components are regarded as the keys that flip a automobile on and off, enhancer sequences are the automobile’s ignition swap. Each components have to work together to make a automobile run, similar to how transcription components have to bind to particular enhancer sequences to specific a gene.
The researchers used new genomic methods known as single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin using sequencing to identify the enhancer sequences and their corresponding transcription factors that play a role in hair cell regeneration.
“Our study identified two families of transcription factors that work together to activate hair cell regeneration in zebrafish, called Sox and Six transcription factors,” said Jimenez.
First, the Sox transcription factors initiate the regeneration response in surrounding cells, called support cells. Next, the Sox and Six transcription factors cooperate to turn those support cells into hair cells.
When hair cells die in zebrafish, nearby support cells start replicating. These support cells are like stem cells because of their ability to become other cell types. Researchers had 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.
“We have identified a unique combination of transcription factors that trigger regeneration in zebrafish. Further down the line, this group of zebrafish transcription factors might become a biological target that may lead to the development of novel therapy to treat hearing loss in humans,” Jimenez said.
Reference: “A regulatory network of Sox and Six transcription factors initiate a cell fate transformation during hearing regeneration in adult zebrafish” by Erin Jimenez, Claire C. Slevin, Wei Song, Zelin Chen, Stephen C. Frederickson, Derek Gildea, Weiwei Wu, Abdel G. Elkahloun, Ivan Ovcharenko and Shawn M. Burgess, 22 August 2022, Cell Genomics.
DOI: 10.1016/j.xgen.2022.100170
The study was funded by the National Human Genome Research Institute.
