Publication Date
1-30-2024
Journal
Proceedings of the National Academy of Sciences of the United States of America
DOI
10.1073/pnas.2304680121
PMID
38266052
PMCID
PMC10835112
PubMedCentral® Posted Date
1-24-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Adult, Animals, Humans, Hair Cells, Auditory, Transcription Factors, Epithelium, Cochlea, Deafness, Mammals, inner ear, reprogramming, hair cells, cochlea
Abstract
Mechanosensory hair cells of the mature mammalian organ of Corti do not regenerate; consequently, loss of hair cells leads to permanent hearing loss. Although nonmammalian vertebrates can regenerate hair cells from neighboring supporting cells, many humans with severe hearing loss lack both hair cells and supporting cells, with the organ of Corti being replaced by a flat epithelium of nonsensory cells. To determine whether the mature cochlea can produce hair cells in vivo, we reprogrammed nonsensory cells adjacent to the organ of Corti with three hair cell transcription factors: Gfi1, Atoh1, and Pou4f3. We generated numerous hair cell–like cells in nonsensory regions of the cochlea and new hair cells continued to be added over a period of 9 wk. Significantly, cells adjacent to reprogrammed hair cells expressed markers of supporting cells, suggesting that transcription factor reprogramming of nonsensory cochlear cells in adult animals can generate mosaics of sensory cells like those seen in the organ of Corti. Generating such sensory mosaics by reprogramming may represent a potential strategy for hearing restoration in humans.
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