PMID- 19261910 OWN - NLM STAT- MEDLINE DCOM- 20090427 LR - 20211020 IS - 0363-6143 (Print) IS - 1522-1563 (Electronic) IS - 0363-6143 (Linking) VI - 296 IP - 3 DP - 2009 Mar TI - Directed differentiation of mouse cochlear neural progenitors in vitro. PG - C441-52 LID - 10.1152/ajpcell.00324.2008 [doi] AB - 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. FAU - Lin, Jizhen AU - Lin J AD - Department of Otolaryngology, 216 Lions Research Bldg., Univ. of Minnesota, 2001 Sixth St. S.E., Minneapolis, MN 55455, USA. linxx004@tc.umn.edu FAU - Feng, Ling AU - Feng L FAU - Hamajima, Yuki AU - Hamajima Y FAU - Komori, Masahiro AU - Komori M FAU - Burns, Terry C AU - Burns TC FAU - Fukudome, Shinji AU - Fukudome S FAU - Anderson, John AU - Anderson J FAU - Wang, Dong AU - Wang D FAU - Verfaillie, Catherine M AU - Verfaillie CM FAU - Low, Walter C AU - Low WC LA - eng GR - R01 DC008165-02/DC/NIDCD NIH HHS/United States GR - R03 CA107989/CA/NCI NIH HHS/United States GR - P30 CD-04660/CD/ODCDC CDC HHS/United States GR - R01 DC008165/DC/NIDCD NIH HHS/United States GR - R01 DC-008165/DC/NIDCD NIH HHS/United States GR - R03 CA-107989/CA/NCI NIH HHS/United States GR - R03 CA107989-02/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Retracted Publication DEP - 20081217 PL - United States TA - Am J Physiol Cell Physiol JT - American journal of physiology. Cell physiology JID - 100901225 RN - 0 (Biomarkers) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Hedgehog Proteins) RN - 0 (Protein Kinase Inhibitors) RN - 5688UTC01R (Tretinoin) RN - 62229-50-9 (Epidermal Growth Factor) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM RIN - Am J Physiol Cell Physiol. 2009 Dec;297(6):C1596. PMID: 19948690 MH - Animals MH - Animals, Newborn MH - Biomarkers/metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cell Culture Techniques MH - *Cell Differentiation/drug effects MH - *Cell Proliferation/drug effects MH - Cell Separation MH - Cells, Cultured MH - Epidermal Growth Factor/metabolism MH - Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/metabolism MH - Hair Cells, Auditory/drug effects/metabolism/*physiology MH - Hedgehog Proteins/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Neurons/drug effects/metabolism/*physiology MH - Organ of Corti/cytology/drug effects/metabolism/*physiology MH - Phenotype MH - Protein Kinase Inhibitors/pharmacology MH - Signal Transduction MH - Stem Cells/drug effects/metabolism/*physiology MH - Time Factors MH - Tretinoin/metabolism PMC - PMC2660259 EDAT- 2009/03/06 09:00 MHDA- 2009/04/28 09:00 PMCR- 2010/03/01 CRDT- 2009/03/06 09:00 PHST- 2009/03/06 09:00 [entrez] PHST- 2009/03/06 09:00 [pubmed] PHST- 2009/04/28 09:00 [medline] PHST- 2010/03/01 00:00 [pmc-release] AID - 00324.2008 [pii] AID - 10.1152/ajpcell.00324.2008 [doi] PST - ppublish SO - Am J Physiol Cell Physiol. 2009 Mar;296(3):C441-52. doi: 10.1152/ajpcell.00324.2008. Epub 2008 Dec 17.