New tool to create lost hearing cells with aging

Summary: Researchers have identified a master gene that programs hair cells in the ear to internal or external cells. The discovery could lead to new treatments to restore hearing loss associated with aging, exposure to noise, or as an adverse reaction to medical therapies.

Source: Northwestern University

Hearing loss due to aging, noise, and certain drugs and antibiotics for cancer therapy have been irreversible because scientists have been unable to reprogram existing cells to become sensory cells. ‘outer and inner ear, essential for hearing, once they die.

But Northwestern Medicine scientists have discovered a single master gene that programs hair cells in the ear externally or internally, overcoming a major obstacle that had prevented the development of these cells to restore hearing.

The study will be published in Nature May 4.

“Our finding provides us with the first clear cell change to make one type against another,” said study lead author Jaime Garcia-Anoveros, a professor of anesthesia, neurology and neuroscience at Northwestern. University Feinberg School of Medicine.

“It will provide a previously unavailable tool for making an internal or external hair cell. We have overcome a major hurdle.”

About 8.5 percent of adults ages 55 to 64 in the U.S. have a hearing loss. This increases to almost 25 percent of those aged 65 to 74 and 50 percent of those aged 75 and over, reports the Centers for Disease Control.

Today, scientists can produce an artificial hair cell, but it is not differentiated into an internal or external cell, which provide different functions essential to producing the ear. The discovery is an important step towards the development of these specific cells.

“It’s like a ballet” as the cells crouch and jump

The death of external hair cells caused by the cochlea is often the cause of deafness and hearing loss. Cells develop in the embryo and do not reproduce. External hair cells expand and contract in response to sound wave pressure and amplify the sound for internal hair cells. Internal cells transmit these vibrations to neurons to create the sounds we hear.

“It’s like a ballet,” Garcia-Anoveros says admiringly as he describes the coordinated movement of internal and external cells. “The exteriors bend down and jump and lift the insides 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 accuracy). Otherwise, the hearing will not take place. ”

Scientists in the Northwest discovered that the programs of the hair cells of the ear are TBX2. When the gene is expressed, the cell becomes an internal hair cell. When the gene is blocked, the cell becomes an external hair cell. The ability to produce one of these cells will require a genetic cocktail, Garcia-Anoveros said.

The ATOH1 and GF1 genes are needed to make a cochlear hair cell from a non-hair hair cell. The TBX2 would then turn on or off to produce the necessary internal or external cell.

The discovery is an important step towards the development of these specific cells. The image is in the public domain

The goal would be to reprogram the support cells, which are intertwined between the hair cells, and provide them with structural support, to the external or internal hair cells.

“We can now find out how to make specifically internal or external hair cells and identify why they are more likely to die and cause deafness,” Garcia-Anoveros said. He stressed that this research is still in the experimental phase.

The article is entitled “Tbx2 is a master regulator of the differentiation and maintenance of internal and external hair cells”.

Other Northwestern authors include lead author Anne Duggan, John C. Clancy, Chuan Zhi Foo, Ignacio Garcia Gomez, Yingji Zhou, Kazuaki Homma, and Mary Ann Cheatham.

About this hearing news and genetic research

Author: Marla Paul
Source: Northwestern University
Contact: Marla Paul – Northwestern University
Image: The image is in the public domain

Original research: Closed access.
“Tbx2 is a master regulator of internal but not external hair cell differentiation” by Jaime García-Añoveros et al. Nature


Summary

See also

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Tbx2 is a master regulator of the differentiation of inner but not outer hair cells

The cochlea uses two types of mechanosensory cells to detect sounds. A single row of internal hair cells (IHC) synapses neurons to transmit sensory information to the brain, and three rows of external hair cells (OHC) selectively amplify auditory inputs.

To date, two transcription factors have been implicated in the specific differentiation of OHCs, while, as far as we know, none have been identified in the differentiation of IHCs.

One of these transcription factors for OHCs, INSM1, acts during a crucial embryonic period to consolidate the fate of the OHC, preventing OHCs from being transdifferentiated into IHC. In the absence of INSM1, embryonic OHCs poorly express a basic set of IHC-specific genes, which we predict are involved in IHC differentiation.

Here we find that one of these genes, Tbx2, is a master regulator of IHC versus OHC differentiation in mice. Ablation of Tbx2 in embryonic IHCs leads to its development as OHC, expressing early markers of OHC such as Insm1 and eventually become fully mature OHCs in the IHC position.

Besides, Tbx2 it is epistatic Insm1: in the absence of both genes, cochleae generate only OHC, suggesting that TBX2 is necessary for abnormal transdifferentiation of INSM1-deficient OHCs into IHC, as well as for normal IHC differentiation. Ablation of Tbx2 in widely differentiated postnatal IHCs, it causes them to be directly transdifferentiated into OHCs, substituting IHC characteristics for those of mature, non-embryonic OHCs.

Finally, ectopic expression of Tbx2 in OHC it results in its transdifferentiation in IHC. So, Tbx2 it is necessary and sufficient to differentiate IHCs from OHCs and to maintain this difference throughout development.

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