title: Differential distribution of stem cells in the auditory and vestibular organs of the inner ear.
abstract: The adult mammalian cochlea lacks regenerative capacity, which is the main reason for the permanence of hearing loss. Vestibular organs, in contrast, replace a small number of lost hair cells. The reason for this difference is unknown. In this work we show isolation of sphere-forming stem cells from the early postnatal organ of Corti, vestibular sensory epithelia, the spiral ganglion, and the stria vascularis. Organ of Corti and vestibular sensory epithelial stem cells give rise to cells that express multiple hair cell markers and express functional ion channels reminiscent of nascent hair cells. Spiral ganglion stem cells display features of neural stem cells and can give rise to neurons and glial cell types. We found that the ability for sphere formation in the mouse cochlea decreases about 100-fold during the second and third postnatal weeks; this decrease is substantially faster than the reduction of stem cells in vestibular organs, which maintain their stem cell population also at older ages. Coincidentally, the relative expression of developmental and progenitor cell markers in the cochlea decreases during the first 3 postnatal weeks, which is in sharp contrast to the vestibular system, where expression of progenitor cell markers remains constant or even increases during this period. Our findings indicate that the lack of regenerative capacity in the adult mammalian cochlea is either a result of an early postnatal loss of stem cells or diminishment of stem cell features of maturing cochlear cells.
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, 801 Welch Road, Stanford, CA 94305-5739, USA.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Oshima
authors.forename: Christian M
authors.initials: CM
authors.lastname: Grimm
authors.forename: C Eduardo
authors.initials: CE
authors.lastname: Corrales
authors.forename: Pascal
authors.initials: P
authors.lastname: Senn
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Martinez Monedero
authors.forename: Gwenaëlle S G
authors.initials: GS
authors.lastname: Géléoc
authors.forename: Albert
authors.initials: A
authors.lastname: Edge
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Holt
authors.forename: Stefan
authors.initials: S
authors.lastname: Heller
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D015415:Biomarkers; D002454:Cell Differentiation; D004594:Electrophysiology; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006198:Hair Cells, Auditory / Q000166:cytology* / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D007473:Ion Channels / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D012038:Regeneration; D012444:Saccule and Utricle / Q000166:cytology* / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D018874:Spheroids, Cellular; D013136:Spiral Ganglion / Q000166:cytology* / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D013316:Stria Vascularis / Q000166:cytology / Q000502:physiology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D049452:Green Fluorescent Proteins; D007473:Ion Channels; C500943:Atoh1 protein, mouse