Epigenetic Barrier Prevents the Regeneration of Inner Ear Cells

Scientists from the University of Southern California have identified a natural barrier to the regeneration of the inner ear’s sensory cells, which are lost in hearing and balance disorders. Overcoming this barrier may be a first step in returning inner ear cells to a newborn-like state that’s primed for regeneration, as described in a new study published in Developmental Cell.

“Permanent hearing loss affects more than 60 percent of the population that reaches retirement age,” said lead researcher Neil Segil. “Our study suggests new gene engineering approaches that could be used to channel some of the same regenerative capability present in embryonic inner ear cells.”

In the supporting cells of the newborn mouse cochlea, the scientists found that hair cell genes were suppressed by both the lack of an activating molecule, H3K27ac, and the presence of the repressive molecule, H3K27me3.  However, at the same time, in the newborn mouse supporting cells, the hair cell genes were kept “primed” to activate by the presence of yet a different histone decoration, H3K4me1. During transdifferentiation of a supporting cell to a hair cell, the presence of H3K4me1 is crucial to activating the correct genes for hair cell development.

With age, the supporting cells of the cochlea gradually lost H3K4me1, causing them to exit the primed state. However, if the scientists added a drug to prevent the loss of H3K4me1, the supporting cells remained temporarily primed for transdifferentiation. Likewise, supporting cells from the vestibular system, which naturally maintained H3K4me1, were still primed for transdifferentiation into adulthood.

“Our study raises the possibility of using therapeutic drugs, gene editing, or other strategies to make epigenetic modifications that tap into the latent regenerative capacity of inner ear cells as a way to restore hearing,” said Segil. “Similar epigenetic modifications may also prove useful in other non-regenerating tissues, such as the retina, kidney, lung, and heart."