NEUROG1 Regulates CDK2 to Promote Proliferation in Otic Progenitors

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

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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. Song and colleagues showed that NEUROG1 promotes proliferation of immortalized multipotent otic progenitor (iMOP) cells by regulating CDK2 expression. The chromatin state at the Cdk2 promoter changes in proliferating and differentiating iMOP cells. NEUROG1-dependent expression of CDK2 correlates with euchromatin marks during proliferation, while heterochromatin marks associate with prevention of CDK2 expression during differentiation.

Original languageEnglish (US)
Pages (from-to)1516-1529
Number of pages14
JournalStem Cell Reports
Issue number5
StatePublished - Nov 14 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology


  • auditory
  • chromatin
  • epigenetics
  • iMOP
  • inner ear
  • neurogenin
  • progenitor
  • spiral ganglion neurons


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