Scientists discover a new mechanism for in-situ regeneration of the cochlear "sound amplifier"

Scientists discover a new mechanism for in-situ regeneration of the cochlear "sound amplifier"

Scientists have discovered a new mechanism of in-situ regenerated cochlear "sound amplifier" Scientists have discovered a new mechanism of in-situ regenerated cochlear "sound amplifier"

The outer hair cells of the cochlea are our sound amplifiers, and the specific expression of the motor protein Prestin can significantly improve our sensitivity to external sound perception
.

The Liu Zhiyong research group of the Center for Excellence in Brain Science and Intelligent Technology of the Chinese Academy of Sciences (Institute of Neuroscience) achieved the first time that the transdifferentiated support cells were Prestin-positive outer hair cells in the cochlea of ​​an adult mouse

eLife

According to reports, various ototoxic drugs, noise, aging and other factors can cause damage to outer hair cells
.

After the hair cells of lower non-mammalian animals are injured, the surrounding supporting cells can transdifferentiate to produce new hair cells

Atoh1 is an important gene in the development of cochlear hair cells
.

Although overexpression of Atoh1 in vivo can transdifferentiate young mouse Sertoli cells into hair cells, unfortunately it cannot convert adult Sertoli cells into hair cells

Atoh1 Atoh1

Ikzf2 is a gene specifically expressed in the outer hair cells of the cochlea, and its functional mutations cause the development of outer hair cells
.

Liu Zhiyong's research group put forward a research hypothesis that simultaneous overexpression of Atoh1 and Ikzf2 can transdifferentiate adult mouse Sertoli cells into Prestin-positive outer hair cells

Ikzf2 Atoh1 Ikzf2

This hypothesis was finally confirmed by experimental results.
Although Atoh1 or Ikzf2 alone cannot transdifferentiate into adult mouse Sertoli cells, Atoh1 and Ikzf2 together can successfully convert adult mouse Sertoli cells into Prestin-positive outer hair cells
.

More encouragingly, the synergistic transdifferentiation efficiency of Atoh1 and Ikzf2 is greatly improved in the outer hair cell injury model, reaching 16%~29%

Atoh1 Ikzf2 Atoh1 Ikzf2 Atoh1 Ikzf2

In order to further determine the characteristics of the newborn outer hair cells, the researchers performed ultra-high-resolution scanning electron microscopy and single-cell transcriptome analysis
.

Studies have shown that the newly-born outer hair cells not only have cilia on the top, but also their gene expression profile is similar to that of wild-type outer hair cells, but is significantly different from other types of inner ear hair cells

"This is the first time that transdifferentiated supporting cells are Prestin-positive outer hair cells in the cochlea of ​​an adult mouse
.

" The eLife peer-reviewed experts commented that this is a milestone and important research achievement in the field of cochlear hair cell regeneration.

eLife

Related paper information: https://doi.

https://doi.
org/10.
7554/eLife.
66547