title: Lgr5-positive supporting cells generate new hair cells in the postnatal cochlea.
abstract: The prevalence of hearing loss after damage to the mammalian cochlea has been thought to be due to a lack of spontaneous regeneration of hair cells, the primary receptor cells for sound. Here, we show that supporting cells, which surround hair cells in the normal cochlear epithelium, differentiate into new hair cells in the neonatal mouse following ototoxic damage. Using lineage tracing, we show that new hair cells, predominantly outer hair cells, arise from Lgr5-expressing inner pillar and third Deiters cells and that new hair cell generation is increased by pharmacological inhibition of Notch. These data suggest that the neonatal mammalian cochlea has some capacity for hair cell regeneration following damage alone and that Lgr5-positive cells act as hair cell progenitors in the cochlea.
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02115, USA ; Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA ; Program in Speech and Hearing Bioscience and Technology, Division of Health Sciences and Technology, Harvard and MIT, Cambridge, MA 02139, USA.
authors.forename: Naomi F
authors.initials: NF
authors.lastname: Bramhall
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02115, USA ; Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.
authors.forename: Fuxin
authors.initials: F
authors.lastname: Shi
authors.affiliation: Massachusetts General Hospital Center for Regenerative Medicine, Boston, MA 02114, USA.
authors.forename: Katrin
authors.initials: K
authors.lastname: Arnold
authors.affiliation: Massachusetts General Hospital Center for Regenerative Medicine, Boston, MA 02114, USA.
authors.forename: Konrad
authors.initials: K
authors.lastname: Hochedlinger
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School, Boston, MA 02115, USA ; Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA ; Program in Speech and Hearing Bioscience and Technology, Division of Health Sciences and Technology, Harvard and MIT, Cambridge, MA 02139, USA.
authors.forename: Albert S B
authors.initials: AS
authors.lastname: Edge
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D049109:Cell Proliferation; D054338:Cell Transdifferentiation; D003051:Cochlea / Q000166:cytology* / Q000378:metabolism*; D005839:Gentamicins / Q000494:pharmacology; D006198:Hair Cells, Auditory / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009925:Organ of Corti / Q000166:cytology / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D051880:Receptors, Notch / Q000037:antagonists & inhibitors / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: D001381:Azepines; D005839:Gentamicins; C493597:Lgr5 protein, mouse; C484278:N2-((2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl)-N1-((7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-L-alaninamide; D043562:Receptors, G-Protein-Coupled; D051880:Receptors, Notch; D055748:SOXB1 Transcription Factors; D053829:Amyloid Precursor Protein Secretases; D000409:Alanine