New research with mice reveals clues that could regrow cells that help us hear.
The most common cause of hearing loss is progressive because cochlear hair cells—the primary cells to detect sound waves—cannot regenerate if damaged or lost. People who have repeated exposure to loud noises, like military personnel, construction workers, and musicians, are most at risk for this type of hearing loss. But, it can happen to anyone over time (even concert goers).
On the other hand, birds and fish can regenerate these hair cells. Now, researchers are getting closer to identifying the mechanisms that may promote this type of regeneration in mammals, as explained in the new study in Frontiers in Cellular Neuroscience.
“We know from our previous work that expression of an active growth gene, called ERBB2, was able to activate the growth of new hair cells (in mammals), but we didn’t fully understand why,” says Patricia White, professor of neuroscience and otolaryngology at the University of Rochester Medical Center.
That previous work, a 2018 study led by Jingyuan Zhang, a postdoctoral fellow in the White lab at the time, found that activating the growth gene ERBB2 pathway triggered a cascading series of cellular events by which cochlear support cells began to multiply and activate other neighboring stem cells to become new sensory hair cells.
“This new study tells us how that activation is happening—a significant advance toward the ultimate goal of generating new cochlear hair cells in mammals,” says White.
Using single-cell RNA sequencing in mice, researchers compared cells with an overactive growth gene (ERBB2 signaling) with similar cells that lacked such signaling. They found the growth gene—ERBB2—promoted stem cell-like development by initiating the expression of multiple proteins—including SPP1, a protein that signals through the CD44 receptor.
The CD44 receptor is known to be present in cochlear-supporting cells. This increase in cellular response promoted mitosis in the supporting cells, a key event for regeneration.
“When we checked this process in adult mice, we were able to show that ERBB2 expression drove the protein expression of SPP1 that is necessary to activate CD44 and grow new hair cells,” says Dorota Piekna-Przybylska, a staff scientist in the White lab and first author of the study.
“This discovery has made it clear that regeneration is not only restricted to the early stages of development. We believe we can use these findings to drive regeneration in adults.”
“We plan to further investigation of this phenomenon from a mechanistic perspective to determine whether it can improve auditory function after damage in mammals. That is the ultimate goal,” says White.
The US Army Medical Research and Development Command (USAMRDC), the National Institute on Deafness and Other Communication Disorders, UR Ventures, and the Schmitt Program on Integrative Neuroscience funded the work.
Source: University of Rochester
