Regenerating hair cells in human vestibular sensory epithelia
- University College London, United Kingdom
- Imperial College London, United Kingdom
- 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)
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Regenerating hair cells in human vestibular sensory epitheliaPublicly available at the NCBI Gene Expression Omnibus (accession no. GSE109320).
Article and author information
Author details
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
- Tanya T. Whitfield, University of Sheffield, United Kingdom
Publication history
- Received: January 4, 2018
- Accepted: July 16, 2018
- Accepted Manuscript published: July 18, 2018 (version 1)
- 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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Regenerating hair cells in human vestibular sensory epithelia
eLife 7:e34817.
https://doi.org/10.7554/eLife.34817
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