Regenerating hair cells in human vestibular sensory epithelia

  1. Ruth Rebecca Taylor  Is a corresponding author
  2. Anastasia Filia
  3. Ursula Paredes
  4. Yukako Asai
  5. Jeffrey R Holt
  6. Michael Lovett
  7. Andrew Forge  Is a corresponding author
  1. University College London, United Kingdom
  2. Imperial College London, United Kingdom
  3. Harvard Medical School, United States

Abstract

Human vestibular sensory epithelia in explant culture were incubated in gentamicin to ablate hair cells. Subsequent transduction of supporting cells with ATOH1 using an Ad-2 viral vector resulted in generation of highly significant numbers of cells expressing the hair cell marker protein myosin VIIa. Cells expressing myosin VIIa were also generated after blocking the Notch signalling pathway with TAPI-1 but less efficiently. Transcriptomic analysis following ATOH1 transduction confirmed up-regulation of 335 putative hair cell marker genes, including several downstream targets of ATOH1. Morphological analysis revealed numerous cells bearing dense clusters of microvilli at the apical surfaces which showed some hair cell-like characteristics confirming a degree of conversion of supporting cells. However, no cells bore organised hair bundles and several expected hair cell markers genes were not expressed suggesting incomplete differentiation. Nevertheless, the results show a potential to induce conversion of supporting cells in the vestibular sensory tissues of humans.

Data availability

All sequencing data from all of these samples have been deposited in NCBI GEO (accession number: GSE109320)

The following data sets were generated

Article and author information

Author details

  1. Ruth Rebecca Taylor

    UCL Ear Institute, University College London, London, United Kingdom
    For correspondence
    Ruth.r.taylor@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  2. Anastasia Filia

    National Heart and Lung Institute, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Ursula Paredes

    UCL Ear Institute, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Yukako Asai

    FM Kirby Neurobiology Center, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jeffrey R Holt

    FM Kirby Neurobiology Center, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Michael Lovett

    National Heart and Lung Institute, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Andrew Forge

    UCL Ear Institute, University College London, London, United Kingdom
    For correspondence
    a.forge@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0995-0219

Funding

Medical Research Council (Project grant,G1000068)

  • Ruth Rebecca Taylor
  • Andrew Forge

Dunhill Medical Trust (Project grant R395/1114)

  • Andrew Forge

Rosetrees Trust (Project grant M58-F1)

  • Andrew Forge

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Ethical approval from NHS Health Research Authority, NRES Committee London -Surrey Borders. REC reference 11/LO/0475; IRAS project ID 73422. Tissue was collected anonymously with informed consent of the patient for tissue harvesting and publication of the results of the study.

Reviewing Editor

  1. Tanya T. Whitfield, University of Sheffield, United Kingdom

Publication history

  1. Received: January 4, 2018
  2. Accepted: July 16, 2018
  3. Accepted Manuscript published: July 18, 2018 (version 1)
  4. Version of Record published: August 6, 2018 (version 2)

Copyright

© 2018, Taylor et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Ruth Rebecca Taylor
  2. Anastasia Filia
  3. Ursula Paredes
  4. Yukako Asai
  5. Jeffrey R Holt
  6. Michael Lovett
  7. Andrew Forge
(2018)
Regenerating hair cells in human vestibular sensory epithelia
eLife 7:e34817.
https://doi.org/10.7554/eLife.34817

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