Identification and characterization of mouse cochlear stem cells.
Genetic, noise- and drug-induced loss of hair cells in the mouse and human cochlea leads to permanent hearing loss due to lack of regeneration of hair cells, which may be due to reduced numbers or loss of the regenerative ability of stem cells in the adult cochlea. We hypothesized that the mouse neonate cochlea harbors stem cells capable of differentiating into hair cells. Cells from the primary neonate cochlear culture began to proliferate and formed floating spheres after 14 days in vitro (DIV). By comparison, spheres from the primary culture of the cortex were observed after 7 DIV. Cochlear sphere cells could be passaged and the new spheres were observed after 7 DIV. Cochlear sphere cells were capable of differentiating into astrocytes and oligodendrocytes, but not neurons under the conditions tested. Cochlear sphere cells expressed Sox2 and Myo7a, but failed to show markers that are expressed exclusively in mature cochlear tissue, while cells from cortex spheres expressed Sox2 and Otx2, but not Myo7a. Our results show that cochleae from neonatal mice harbor cells capable of forming spheres and cells from these spheres appear to be better endowed to become hair cells.
Yerukhimovich
Michael V
MV
Department of Otolaryngology, Head and Neck Surgery, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Bai
Lianhua
L
Chen
Daniel H-C
DH
Miller
Robert H
RH
Alagramam
Kumar N
KN
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D003051:Cochlea / Q000166:cytology* / Q000502:physiology; D004398:Dyneins / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006198:Hair Cells, Auditory / Q000166:cytology; D018398:Homeodomain Proteins / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018874:Spheroids, Cellular; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D050821:Transcription Factor Brn-3C / Q000235:genetics
D018398:Homeodomain Proteins; D007381:Intermediate Filament Proteins; C000631455:MYO7A protein, human; C000631456:Myo7a protein, mouse; D000081412:Myosin VIIa; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; C121290:Pou4f3 protein, mouse; D050821:Transcription Factor Brn-3C; D009218:Myosins; D004398:Dyneins