Confocal picture of grownup zebrafish hair cells (inexperienced) within the auditory organ of the interior ear. Credit: Erin Jimenez, Ph.D.
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A examine demonstrates how transcription components help cell regeneration.
Researchers on the National Institutes of Health have recognized a selected protein community that’s mandatory for cell regeneration to revive listening to in zebrafish. Researchers on the National Human Genome Research Institute (NHGRI) led the analysis, which can assist in the creation of human listening to loss remedies. The findings had been not too long ago revealed within the journal Cell Genomics.
Many animals, like zebrafish, might recuperate their listening to after harm by means of the regeneration of hair cells, nonetheless, human hair cell loss can’t be restored. The regenerating properties of zebrafish hair cells impressed researchers to make use of this species to raised perceive sure elementary properties of regeneration.
About 37.5 million Americans undergo from listening to loss, and nearly all of these cases 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 by means of nerves and into our brains that permit us to course of sound.
Despite 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 raised 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: Erin Jimenez, Ph.D.
Erin Jimenez, Ph.D., a postdoctoral fellow within the laboratory of Shawn Burgess, Ph.D., senior investigator within the National Human Genome Research Institute’s (NHGRI) Translational and Functional Genomics Branch, led the examine in collaboration with researchers Ivan Ovcharenko, Ph.D., and Wei Song, Ph.D., on the National Library of Medicine’s National Center for Biotechnology Information.
“Humans and other mammals are born with a set number of hair cells that are slowly lost through aging and trauma. However some animals, such as zebrafish, can regenerate hair cells and recover hearing after injury,” stated Burgess. “How and why regeneration happens in these animals remains a mystery that many scientists would like to unravel.”
Using a mix of genomic strategies 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, often known as transcription components. To correctly establish which transcription components had been at play, the researchers first had to have a look at the enhancer sequences inside the zebrafish genome.
If transcription components are considered the keys that flip a automotive on and off, enhancer sequences are the automotive’s ignition swap. Both elements have to work together to make a automotive run, similar to how transcription components have to bind to particular enhancer sequences to precise a gene.
The researchers used new genomic strategies 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.
