Affiliation:
1. Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030
2. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030
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.
Funder
HHS | NIH | National Institute on Deafness and Other Communication Disorders
Cancer Prevention and Research Institute of Texas
HHS | NIH | National Cancer Institute
HHS | NIH | National Center for Research Resources
Publisher
Proceedings of the National Academy of Sciences