NEUROG1 Regulates CDK2 to Promote Proliferation in Otic Progenitors

Zhichao Song; Azadeh Jadali; Bernd Fritzsch; Kelvin Y Kwan

doi:10.1016/j.stemcr.2017.09.011

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NEUROG1 Regulates CDK2 to Promote Proliferation in Otic Progenitors

Journal article

Open access

Peer reviewed

NEUROG1 Regulates CDK2 to Promote Proliferation in Otic Progenitors

Zhichao Song, Azadeh Jadali, Bernd Fritzsch and Kelvin Y Kwan

Stem cell reports, Vol.9(5), pp.1516-1529

11/14/2017

DOI: 10.1016/j.stemcr.2017.09.011

PMCID: PMC5829327

PMID: 29033307

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Abstract

Loss of spiral ganglion neurons (SGNs) significantly contributes to hearing loss. Otic progenitor cell transplantation is a potential strategy to replace lost SGNs. Understanding how key transcription factors promote SGN differentiation in otic progenitors accelerates efforts for replacement therapies. A pro-neural transcription factor, Neurogenin1 (Neurog1), is essential for SGN development. Using an immortalized multipotent otic progenitor (iMOP) cell line that can self-renew and differentiate into otic neurons, NEUROG1 was enriched at the promoter of cyclin-dependent kinase 2 (Cdk2) and neurogenic differentiation 1 (NeuroD1) genes. Changes in H3K9ac and H3K9me3 deposition at the Cdk2 and NeuroD1 promoters suggested epigenetic regulation during iMOP proliferation and differentiation. In self-renewing iMOP cells, overexpression of NEUROG1 increased CDK2 to drive proliferation, while knockdown of NEUROG1 decreased CDK2 and reduced proliferation. In iMOP-derived neurons, overexpression of NEUROG1 accelerated acquisition of neuronal morphology, while knockdown of NEUROG1 prevented differentiation. Our findings suggest that NEUROG1 can promote proliferation or neuronal differentiation.

Cyclin-Dependent Kinase 2 - metabolism

Basic Helix-Loop-Helix Transcription Factors - genetics

Cell Proliferation

Cells, Cultured

Cyclin-Dependent Kinase 2 - genetics

Neural Stem Cells - physiology

Neural Stem Cells - cytology

Nerve Tissue Proteins - genetics

Neurogenesis

Spiral Ganglion - cytology

Nerve Tissue Proteins - metabolism

Animals

Basic Helix-Loop-Helix Transcription Factors - metabolism

Histone Code

Mice

Neural Stem Cells - metabolism

Details

Title: Subtitle: NEUROG1 Regulates CDK2 to Promote Proliferation in Otic Progenitors
Creators: Zhichao Song - Department of Cell Biology & Neuroscience, Rutgers University, Piscataway, NJ 08854, USA; Stem Cell Research Center and Keck Center for Collaborative Neuroscience, Rutgers University, Piscataway, NJ 08854, USA
Azadeh Jadali - Department of Cell Biology & Neuroscience, Rutgers University, Piscataway, NJ 08854, USA; Stem Cell Research Center and Keck Center for Collaborative Neuroscience, Rutgers University, Piscataway, NJ 08854, USA
Bernd Fritzsch - Department of Biology, University of Iowa, CLAS, 214 BB, Iowa City, IA 52242, USA
Kelvin Y Kwan - Department of Cell Biology & Neuroscience, Rutgers University, Piscataway, NJ 08854, USA; Stem Cell Research Center and Keck Center for Collaborative Neuroscience, Rutgers University, Piscataway, NJ 08854, USA. Electronic address: kwan@dls.rutgers.edu
Resource Type: Journal article
Publication Details: Stem cell reports, Vol.9(5), pp.1516-1529
DOI: 10.1016/j.stemcr.2017.09.011
PMID: 29033307
PMCID: PMC5829327
NLM abbreviation: Stem Cell Reports
ISSN: 2213-6711
eISSN: 2213-6711
Publisher: United States
Grant note: R01 DC015000 / NIDCD NIH HHS
Language: English
Date published: 11/14/2017
Academic Unit: Iowa Neuroscience Institute; Biology; Craniofacial Anomalies Research Center
Record Identifier: 9984070875102771

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