DNA methylation in the mouse cochlea promotes maturation of supporting cells and contributes to the failure of hair cell regeneration
Abstract
Age-related hearing loss can significantly impact quality of life. One potential approach to restore hearing is to regenerate mechanosensory hair cells responsible for detecting sound by the conversion of neighboring supporting cells into new hair cells. However, mammalian supporting cells can only transdifferentiate during embryonic and early postnatal development, and this ability is lost before the onset of hearing. We show that supporting cells accumulate DNA methylation, a form of epigenetic silencing, to permanently shut off the hair cell gene program required for successful transdifferentiation. Blocking ten-eleven translocation (TET) enzyme activity extends the window in which transdifferentiation can occur. Moreover, the loss of hair cells by deafening partially reverses DNA methylation in supporting cells, suggesting one avenue for therapeutic intervention.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- August 2023
- DOI:
- 10.1073/pnas.2300839120
- Bibcode:
- 2023PNAS..12000839N