Hearing loss is the most common loss of sensation. Most cases of hearing loss are due to the death of specialized hair cells found deep inside the ear.

These hair cells convert sounds into nerve impulses which can be understood by the brain. Hair cells naturally degrade as part of aging and can be damaged by other factors including loud noises, and otherwise therapeutic drugs, such as those used in chemotherapy for cancer. In humans and other mammals, once hair cells are lost they cannot be replaced.

Hair cells have often been studied using mice, but the small number of hair cells in their ears, and their location deep inside the skull, makes it particularly difficult to study them in this way. Scientists are seeking ways to grow hair cells in the laboratory to make it easier to understand how they work and the factors that contribute to their damage and loss.

Different cell types in the body are formed in response to specific combinations of biological signals. Currently, scientists do not have an efficient way to grow hair cells in the laboratory, because the correct signals needed to create them are not known.

Induced Hair Cells

UCLA’s Louise Menendez and colleagues have now identified four proteins which, when activated, convert fibroblasts, a common type of cell, into hair cells similar to those in the ear. These proteins are called Six1, Atoh1, Pou4f3 and Gfi1.

The researchers have termed the resulting cells induced hair cells, or iHCs for short, and analyzed these cells to identify those characteristics that are similar to normal hair cells, as well as their differences. Importantly, the iHCs were found to be damaged by the same chemicals that specifically harm normal hair cells, suggesting they are useful test subjects.

[caption id=“attachment_103316” align=“aligncenter” width=“700”]induced auditory hair cells Overexpression of Six1, Atoh1, Pou4f3 and Gfi1 is capable of activating hair cell markers in mouse embryonic fibroblasts.
Credit: L Menendez, et al CC-BY[/caption]

The ability to create hair cells in the laboratory using more easily available cells has many uses. These cells can help to understand the normal function of hair cells and how they become damaged.

They can also be used to test new drugs to assess their success in preventing or reversing hearing loss. These findings may also lead to genetic solutions to curing hearing loss.

[1] Louise Menendez, Talon Trecek, Suhasni Gopalakrishnan, Litao Tao, Alexander L Markowitz, Haoze V Yu, Xizi Wang, Juan Llamas, Chichou Huang, James Lee, Radha Kalluri, Justin Ichida, Neil Segil. Generation of inner ear hair cells by direct lineage conversion of primary somatic cells. eLife 2020;9:e55249 DOI: 10.7554/eLife.55249

Top Image: Hair cells (green) from a newborn mouse. Credit: Yassan Abdolazimi CC BY

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