In humans, hearing loss from exposure to loud noises is progressive because the primary cells which detect sound, cochlear hair cells, 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, though it can happen to anyone over time.
On the other hand, birds and fish can regenerate these hair cells, and now researchers report their advances in promoting this effect in mammals. Their work is published 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,” said Patricia White, PhD, professor of Neuroscience and Otolaryngology at the University of Rochester Medical Center. The 2018 study led by Jingyuan Zhang, PhD, 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 neighbouring 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,” said White.
Using single-cell RNA sequencing in mice, researchers compared cells with an overactive growth gene (ERBB2 signalling) with similar cells that lacked such signalling. 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,” said Dorota Piekna-Przybylska, PhD, 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,” said White.
