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Thursday, May 26, 2022

New Tool To Create Ear Hair Cells Lost Due to Aging or Noise

According to a new study, scientists have uncovered a single master gene that programs ear hair cells into either outer or inner ones, overcoming a major hurdle that had prevented the development of these cells to restore hearing.

‘We have overcome a major hurdle’ to restore hearing, investigators say.

  • Gene discovery allows the production of inner or outer ear hair cells
  • Death of outer hair cells due to aging or noise cause most hearing loss
  • Master gene switch turns on ear hair cell development

Hearing loss caused by aging, noise, and some cancer therapy medications and antibiotics has been irreversible because scientists have not been able to reprogram existing cells to develop into the outer and inner ear sensory cells — essential for hearing — once they die.

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

“Our finding gives us the first clear cell switch to make one type versus the other,” 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 provide a previously unavailable tool to make an inner or outer hair cell. We have overcome a major hurdle.”

About 8.5% of adults aged 55 to 64 in the U.S. have disabling hearing loss. That increases to nearly 25% of those aged 65 to 74 and 50% of those who are 75 and older, 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 different essential functions to produce hearing. The discovery is a major step toward developing these specific cells.

‘It’s like a ballet’ as cells crouch and leap

The death of outer hair cells made by the cochlea is most often 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 from sound waves and amplify sound for the inner hair cells. The inner cells transmit those vibrations to the neurons to create the sounds we hear.

Jaime García-Añoveros

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 with awe as he describes the coordinated movement of the inner and outer cells. “The outers crouch and jump and lift the inners further into the ear. 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.”

The master gene switch Northwestern scientists discovered that programs the ear hair cells is 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 one of these cells will require a gene cocktail, García-Añoveros said. The ATOH1 and GF1 genes are needed to make a cochlear hair cell from a non-hair cell. Then the TBX2 would be turned on or off to produce the needed inner or outer cell.

The goal would be to reprogram supporting cells, which are latticed among the hair cells and provide them with structural support, into outer or inner hair cells.

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

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, 4 May 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 and 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 the National Institute of Deafness and other Communications Disorders grants R01 DC015903 and R01 DC019834.

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