Helios is a key transcriptional regulator of outer hair cell maturation

Lauren Chessum, Maggie S. Matern, Michael C. Kelly, Stuart L. Johnson, Yoko Ogawa, Beatrice Milon, Mark McMurray, Elizabeth C. Driver, Andrew Parker, Yang Song, Gemma Codner, Christopher T. Esapa, Jack Prescott, Graham Trent, Sara Wells, Abigail K. Dragich, Gregory I. Frolenkov, Matthew W. Kelley, Walter Marcotti, Steve D. M. Brown, Ran Elkon, Michael R. Bowl () and Ronna Hertzano ()
Additional contact information
Lauren Chessum: MRC Harwell Institute
Maggie S. Matern: University of Maryland School of Medicine
Michael C. Kelly: National Institutes of Health
Stuart L. Johnson: University of Sheffield
Yoko Ogawa: University of Maryland School of Medicine
Beatrice Milon: University of Maryland School of Medicine
Mark McMurray: University of Maryland School of Medicine
Elizabeth C. Driver: National Institutes of Health
Andrew Parker: MRC Harwell Institute
Yang Song: University of Maryland School of Medicine
Gemma Codner: MRC Harwell Institute
Christopher T. Esapa: MRC Harwell Institute
Jack Prescott: MRC Harwell Institute
Graham Trent: University of Maryland School of Medicine
Sara Wells: MRC Harwell Institute
Abigail K. Dragich: University of Kentucky
Gregory I. Frolenkov: University of Kentucky
Matthew W. Kelley: National Institutes of Health
Walter Marcotti: University of Sheffield
Steve D. M. Brown: MRC Harwell Institute
Ran Elkon: Sackler School of Medicine, Tel Aviv University
Michael R. Bowl: MRC Harwell Institute
Ronna Hertzano: University of Maryland School of Medicine

Nature, 2018, vol. 563, issue 7733, 696-700

Abstract: Abstract The sensory cells that are responsible for hearing include the cochlear inner hair cells (IHCs) and outer hair cells (OHCs), with the OHCs being necessary for sound sensitivity and tuning1. Both cell types are thought to arise from common progenitors; however, our understanding of the factors that control the fate of IHCs and OHCs remains limited. Here we identify Ikzf2 (which encodes Helios) as an essential transcription factor in mice that is required for OHC functional maturation and hearing. Helios is expressed in postnatal mouse OHCs, and in the cello mouse model a point mutation in Ikzf2 causes early-onset sensorineural hearing loss. Ikzf2cello/cello OHCs have greatly reduced prestin-dependent electromotile activity, a hallmark of OHC functional maturation, and show reduced levels of crucial OHC-expressed genes such as Slc26a5 (which encodes prestin) and Ocm. Moreover, we show that ectopic expression of Ikzf2 in IHCs: induces the expression of OHC-specific genes; reduces the expression of canonical IHC genes; and confers electromotility to IHCs, demonstrating that Ikzf2 can partially shift the IHC transcriptome towards an OHC-like identity.

Keywords: Outer Hair Cells (OHCs); Helios; Inner Hair Cells (IHCs); Prestin; Distortion Product Oto Acoustic Emissions (DPOAE) (search for similar items in EconPapers)
Date: 2018
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Citations: View citations in EconPapers (2)

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DOI: 10.1038/s41586-018-0728-4

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