Abstract
Multipotent cochlear neural progenitors (CNPs) in the organ of Corti hold the promise for cell replacement in degenerative hearing disorders. However, not much is known about the CNPs and the specific conditions for their differentiation. Here we isolate the CNPs from the postnatal day 1 organ of Corti in mice and demonstrate their capability to self-renew and to differentiate into hair cell-like and neuronal cell-like phenotypes under the guidance of sonic hedgehog (SHH), epidermal growth factor (EGF), retinoic acid (RA), and brain-derived neurotrophic factor (BDNF), herein termed SERB (abbreviation of SHH, EGF, RA, and BDNF) in an asymmetric or symmetric manner from clonal isolates. Differentiation of CNPs into hair cells by SERB was dependent on the ERK signaling pathway, whereas the differentiation of CNPs into neurons by SERB was not. This work develops a new in vitro methodology for the maintenance and self-regeneration of CNPs for future design of regenerative strategies for hearing disorders.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Retracted Publication
MeSH terms
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Animals
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Animals, Newborn
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Biomarkers / metabolism
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Brain-Derived Neurotrophic Factor / metabolism
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Cell Culture Techniques
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Cell Differentiation* / drug effects
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Cell Proliferation* / drug effects
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Cell Separation
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Cells, Cultured
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Epidermal Growth Factor / metabolism
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Hair Cells, Auditory / drug effects
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Hair Cells, Auditory / metabolism
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Hair Cells, Auditory / physiology*
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Hedgehog Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Neurons / drug effects
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Neurons / metabolism
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Neurons / physiology*
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Organ of Corti / cytology
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Organ of Corti / drug effects
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Organ of Corti / metabolism
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Organ of Corti / physiology*
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Phenotype
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Protein Kinase Inhibitors / pharmacology
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Signal Transduction
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Stem Cells / drug effects
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Stem Cells / metabolism
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Stem Cells / physiology*
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Time Factors
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Tretinoin / metabolism
Substances
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Biomarkers
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Brain-Derived Neurotrophic Factor
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Hedgehog Proteins
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Protein Kinase Inhibitors
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Tretinoin
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Epidermal Growth Factor
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Extracellular Signal-Regulated MAP Kinases