Directed differentiation of mouse cochlear neural progenitors in vitro.
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.
Lin
Jizhen
J
Department of Otolaryngology, 216 Lions Research Bldg., Univ. of Minnesota, 2001 Sixth St. S.E., Minneapolis, MN 55455, USA. linxx004@tc.umn.edu
Feng
Ling
L
Hamajima
Yuki
Y
Komori
Masahiro
M
Burns
Terry C
TC
Fukudome
Shinji
S
Anderson
John
J
Wang
Dong
D
Verfaillie
Catherine M
CM
Low
Walter C
WC
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D053823:Hedgehog Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009925:Organ of Corti / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D014212:Tretinoin / Q000378:metabolism
D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D053823:Hedgehog Proteins; D047428:Protein Kinase Inhibitors; D014212:Tretinoin; D004815:Epidermal Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases