Scientists find ‘master gene’ to regrow lost ear hair cells for restoring hearing in mice

Death of outer hair cells made by ear’s cochlea is most often cause of hearing loss, scientists say

Scanning electron microscope image of the hair bundles of inner and outer hair cells from the mouse cochlea (Tobias Bartsch)

Scientists have discovered a single “master gene” that programmes ear hair cells into either outer or inner ones, an advance that they say can help overcome a major hurdle to restoring hearing.

Researchers, including those from Northwestern University in the US, say hearing loss either due to aging, noise, or certain cancer therapy drugs and antibiotics, has been irreversible since effective methods do not exist for reprogramming existing cells to develop into the outer and inner ear sensory cells – essential for hearing – once they die.

While currently there are ways to produce artificial hair cells, scientists say these do not differentiate the hair cells into inner or outer ear cells, which provide different essential functions to produce hearing.

The new discovery, published in the journal Nature last week, is a major step towards developing these specific cells, scientists say.

“Our finding gives us the first clear cell switch to make one type versus the other. It will provide a previously unavailable tool to make an inner or outer hair cell. We have overcome a major hurdle,” study lead author Jaime García-Añoveros from Northwestern University said in a statement.

About 8.5 per cent of adults aged 55 to 64 in the US have disabling hearing loss, a number that increases to nearly 25 per cent of those aged 65 to 74, and 50 per cent of those who are 75 and older, according to the US Centers for Disease Control and Prevention (CDC).

Most often, the cause of deafness and hearing loss is the death of outer hair cells made by the ear’s cochlea, which develop in the embryo and do not reproduce, researchers have said.

These cells expand and contract in response to the pressure from sound waves and amplify sound for the inner hair cells, while the inner cells transmit those vibrations to the neurons to create the sounds we hear, studies have shown.

“It’s like a ballet. The outers crouch and jump and lift the inners further into the ear,” Dr García-Añoveros said. “The ear is a beautiful organ. There is no other organ in a mammal where the cells are so precisely positioned. (I mean, with micrometric precision). Otherwise, hearing doesn’t occur.”

In the new study, scientists found that a “master gene” TBX2 programmes the ear hair cells in mice.

They found that when the TBX2 gene is expressed, the cell becomes an inner hair cell, and when it is blocked, the cell becomes an outer hair cell.

Researchers also found that a cocktail of genes – ATOH1 and GF1 – are needed to make a cochlear hair cell from a non-hair cell, and then the TBX2 would be turned on or off to produce the needed inner or outer cell.

In further studies, scientists hope to “figure out how to make specifically inner or outer hair cells and identify why the latter are more prone to dying and cause deafness”.