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Helios is a key transcriptional regulator of outer hair cell maturation

Author

Listed:
  • 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
    Tel Aviv University)

  • Michael R. Bowl

    (MRC Harwell Institute)

  • Ronna Hertzano

    (University of Maryland School of Medicine
    University of Maryland School of Medicine
    University of Maryland School of Medicine)

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.

Suggested Citation

  • 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., 2018. "Helios is a key transcriptional regulator of outer hair cell maturation," Nature, Nature, vol. 563(7733), pages 696-700, November.
    • Handle: RePEc:nat:nature:v:563:y:2018:i:7733:d:10.1038_s41586-018-0728-4
    DOI: 10.1038/s41586-018-0728-4
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    Cited by:

    1. Marina Kaiser & Timo H. Lüdtke & Lena Deuper & Carsten Rudat & Vincent M. Christoffels & Andreas Kispert & Mark-Oliver Trowe, 2022. "TBX2 specifies and maintains inner hair and supporting cell fate in the Organ of Corti," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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