News Statement
14 September 2022 on Wednesday
The importance of transcription factors in promoting cell regeneration is demonstrated by an NIH study.
Researchers at the National Institutes of Health have identified a unique network of proteins crucial for restoring zebrafish hearing through cell regeneration. The study, coordinated by researchers from the National Human Genome Research Institute (NHGRI), may contribute to the discovery of remedies for human hearing loss. The results were reported in Cell Genomics.
Although hair cell loss cannot be restored in humans, many animals, notably zebrafish, can regenerate hair cells to restore hearing following injury. The regenerating properties of zebrafish hair cells motivated researchers to employ this animal in an effort to comprehend the underlying features of regeneration.
Hearing loss affects around 37.5 million Americans, with the majority of instances resulting from the loss of “hair cells” in the inner ear. The movement and bending of the bristles protruding from these small hair cells in response to sound entering our ears results in the transmission of electrical signals to our nerves and brains, allowing us to process sound.
On a genetic level, humans and zebrafish share more than 70% of their genes, despite their vastly different appearance. This chromosomal similarity affords researchers the opportunity to comprehend the biology of cell regeneration in zebrafish before applying their results to humans.
Erin Jimenez, Ph.D., a postdoctoral fellow in the laboratory of Shawn Burgess, Ph.D., senior investigator in the National Human Genome Research Institute’s (NHGRI) Translational and Functional Genomics Branch, led the study in collaboration with researchers Ivan Ovcharenko, Ph.D., and Wei Song, Ph.D., at the National Center for Biotechnology Information of the National Library of Medicine.
“Humans and other mammals are born with a predetermined amount of hair cells, which are gradually destroyed with age and trauma. “However, other animals, such as zebrafish, are able to rebuild hair cells and recover hearing following injury,” explained Burgess. How and why these animals regenerate remains a conundrum that many scientists would like to solve.
Jimenez and her colleagues discovered, using a mix of genomic approaches and computational-based machine learning, that hair cell regeneration in zebrafish is dependent on a network of transcription factors, proteins that can switch genes on and off. The researchers had to examine the enhancer sequences inside the zebrafish genome before they could determine which transcription factors were at play.
If transcription factors be compared to the keys used to start and stop an automobile, then enhancer sequences are the ignition switch. To make an automobile run, both components must interact, just as transcription factors must bind to certain enhancer regions for a gene to be expressed.
Researchers used single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin sequencing to uncover hair cell regeneration-related enhancer sequences and transcription factors.
“Our research found two families of transcription factors, Sox and Six, that cooperate to drive hair cell regeneration in zebrafish,” stated Jimenez.
First, the Sox transcription factors activate the regeneration response in the support cells that surround the affected cells. The Sox and Six transcription factors then work together to transform the support cells into hair cells.
When zebrafish hair cells die, adjacent support cells begin reproducing. These support cells are similar to stem cells in that they can differentiate into other cell types. Researchers had identified some of the factors responsible for the transformation of support cells into hair cells, but it was unclear how and where the genes encoding these factors are activated and coordinated with other unknown factors.
“We have found a novel combination of transcription factors that induce zebrafish regeneration. This collection of zebrafish transcription factors could become a biological target in the future, which could lead to the creation of a novel medication to treat human hearing loss, Jimenez added.
The National Human Genome Research Institute (NHGRI) is one of the 27 institutes and centers that make up the National Institutes of Health (NIH), a branch of the Department of Health and Human Services. The Division of Intramural Research of the National Human Genome Research Institute develops and implements technologies to investigate, diagnose, and cure genomic and genetic illnesses. There is more information on NHGRI available at https://www.genome.gov.
NIH stands for the National Institutes of Health. The National Institutes of Health (NIH), the nation’s medical research organization, consists of 27 Institutes and Centers and is part of the U.S. Department of Health and Human Services. The NIH is the principal government organization that conducts and supports basic, clinical, and translational medical research and investigates the causes, treatments, and cures for both common and rare diseases. Visit www.nih.gov for more information on the NIH and its initiatives.
NIH…Transforming Research Into Health®
References
Erin Jimenez, Claire C. Slevin, Wei Song, Zelin Chen, Stephen C. Frederickson, Derek Gildea, Weiwei Wu, Abdel G. Elkahloun, Ivan Ovcharenko, Shawn M. Burgess.
During adult zebrafish hearing regeneration, a network of Sox and Six transcription factors initiates a shift in cell destiny. Cell Genomics, 2022. https://doi.org/10.1016/j.xgen.2022.100170.
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