New tool to create ear hair cells lost to aging or noise

According to a new study, scientists have discovered a single main gene that programs ear hair cells into outer or inner, overcoming a major hurdle that had prevented the development of these cells from restoring hearing.

“We’ve passed a major hurdle” to restore hearing, researchers say.

  • Gene discovery enables the production of inner or outer ear hair cells
  • Death of outer hair cells from aging or noise causes most hearing loss
  • Master gene switch turns on ear hair cell development

Hearing loss caused by aging, noise and some cancer therapy drugs and antibiotics is irreversible because scientists have been unable to reprogram existing cells to develop into the sensory cells of the outer and inner ear – essential for hearing – once they die to be.

But Northwestern Medicine scientists have discovered a single main gene that programs ear hair cells into outer or inner, overcoming a major hurdle that previously prevented the development of these cells from restoring hearing, according to new research published today (May 4). 2022). ) in the news Nature

“Our finding gives us the first clear cell switch to make one type versus another,” said lead study author Jaime García-Añoveros, PhD, Professor of Anesthesiology and Neuroscience and in the Ken and Ruth Davee Department of Neurology. “It will be a previously unavailable tool to create an inner or outer hair cell. We have overcome a major hurdle.”

About 8.5% of adults aged 55 to 64 in the US have disabling hearing loss. That rises to nearly 25% of 65- to 74-year-olds and 50% of those over 75, reports the Centers for Disease Control (CDC).

Currently, scientists can produce an artificial hair cell, but it does not differentiate into an inner or outer cell, each of which provides several essential functions to produce hearing. The discovery is a big step towards the development of these specific cells.

‘It’s like a ballet’ when cells squat and jump

The death of the outer hair cells by the cochlea is usually the cause of deafness and hearing loss. The cells develop in the embryo and do not reproduce. The outer hair cells expand and contract in response to the pressure of sound waves and amplify the sound for the inner hair cells. The inner cells transmit those vibrations to the neurons to create the sounds we hear.

Jaime Garcia-Yoveros

Jaime García-Añoveros PhD, professor of anesthesiology, neurology and neuroscience, and lead author of the study published in Nature. Credit: Northwestern University

“It’s like a ballet,” García-Añoveros says in awe as he describes the coordinated movement of the inner and outer cells. “The outer squat and jump and lift the inner further into the ear. The ear is a beautiful organ. There is no other organ in a mammal where the cells are positioned so precisely. (I mean, with micrometric precision). Otherwise the hearing will not take place.”

The master gene switch Northwestern scientists discovered that programs are the ear hair cells TBX2† When the gene is expressed, the cell becomes an inner hair cell. When the gene is blocked, the cell becomes an outer hair cell. The ability to produce any of these cells requires a gene cocktail, García-Añoveros said. The ATOH1 and GF1 genes are needed to turn a non-hairy cell into a cochlear hair cell. Then the TBX2 would be turned on or off to produce the required indoor or outdoor cell.

The goal would be to reprogram supporting cells located between hair cells and provide them with structural support, into outer or inner hair cells.

“We can now figure out how to specifically make inner or outer hair cells and identify why the latter are more prone to dying and causing deafness,” García-Añoveros said. He emphasized that this research is still in the experimental phase.

Reference: “Tbx2 is a master regulator of inner versus outer hair cell differentiation” by Jaime García-Añoveros, John C. Clancy, Chuan Zhi Foo, Ignacio García-Gómez, Yingjie Zhou, Kazuaki Homma, Mary Ann Cheatham, and Anne Duggan, May 4 2022, Nature
DOI: 10.1038/s41586-022-04668-3

Other Northwestern authors include co-lead author Anne Duggan, PhD, research assistant professor of anesthesiology; John C. Clancy, research technician in the García-Añoveros en Duggan laboratory; Chuan Zhi Foo, a graduate student in the Driskill Graduate Program in Life Sciences (DGP); Ignacio García Gómez, PhD, research assistant professor of anesthesiology; Yingji Zhou, PhD, research assistant professor of Neurology; Kazuaki Homma, PhD, Assistant Professor of Otolaryngology – Head and Neck Surgery; and Mary Ann Cheatham, PhD, research professor of communications in the Weinberg College of Arts and Sciences.

The study was funded by National Institute of Deafness and other Communications Disorders grants R01 DC015903 and R01 DC019834.

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