Regeneration of Stereocilia of Hair Cells by Forced Atoh1 Expression in the Adult Mammalian Cochlea

Shi Ming Yang, Wei Chen, Wei Wei Guo, Shuping Jia, Jian He Sun, Hui Zhan Liu, Wie Yen Young, David Z. He

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

The hallmark of mechanosensory hair cells is the stereocilia, where mechanical stimuli are converted into electrical signals. These delicate stereocilia are susceptible to acoustic trauma and ototoxic drugs. While hair cells in lower vertebrates and the mammalian vestibular system can spontaneously regenerate lost stereocilia, mammalian cochlear hair cells no longer retain this capability. We explored the possibility of regenerating stereocilia in the noise-deafened guinea pig cochlea by cochlear inoculation of a viral vector carrying Atoh1, a gene critical for hair cell differentiation. Exposure to simulated gunfire resulted in a 60-70 dB hearing loss and extensive damage and loss of stereocilia bundles of both inner and outer hair cells along the entire cochlear length. However, most injured hair cells remained in the organ of Corti for up to 10 days after the trauma. A viral vector carrying an EGFP-labeled Atoh1 gene was inoculated into the cochlea through the round window on the seventh day after noise exposure. Auditory brainstem response measured one month after inoculation showed that hearing thresholds were substantially improved. Scanning electron microscopy revealed that the damaged/lost stereocilia bundles were repaired or regenerated after Atoh1 treatment, suggesting that Atoh1 was able to induce repair/regeneration of the damaged or lost stereocilia. Therefore, our studies revealed a new role of Atoh1 as a gene critical for promoting repair/regeneration of stereocilia and maintaining injured hair cells in the adult mammal cochlea. Atoh1-based gene therapy, therefore, has the potential to treat noise-induced hearing loss if the treatment is carried out before hair cells die.

Original languageEnglish
Article numbere46355
JournalPLoS One
Volume7
Issue number9
DOIs
StatePublished - Sep 27 2012

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Stereocilia
Cochlea
hairs
Regeneration
Cells
Audition
hearing
cells
Noise-Induced Hearing Loss
Genes
Outer Auditory Hair Cells
Inner Auditory Hair Cells
Noise
Repair
Auditory Hair Cells
Organ of Corti
Gene therapy
Mammals
gene therapy
genes

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Regeneration of Stereocilia of Hair Cells by Forced Atoh1 Expression in the Adult Mammalian Cochlea. / Yang, Shi Ming; Chen, Wei; Guo, Wei Wei; Jia, Shuping; Sun, Jian He; Liu, Hui Zhan; Young, Wie Yen; He, David Z.

In: PLoS One, Vol. 7, No. 9, e46355, 27.09.2012.

Research output: Contribution to journalArticle

Yang, Shi Ming ; Chen, Wei ; Guo, Wei Wei ; Jia, Shuping ; Sun, Jian He ; Liu, Hui Zhan ; Young, Wie Yen ; He, David Z. / Regeneration of Stereocilia of Hair Cells by Forced Atoh1 Expression in the Adult Mammalian Cochlea. In: PLoS One. 2012 ; Vol. 7, No. 9.
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