Regenerating hair cells in vestibular sensory epithelia from humans

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...

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Main Authors: Ruth Rebecca Taylor, Anastasia Filia, Ursula Paredes, Yukako Asai, Jeffrey R Holt, Michael Lovett, Andrew Forge
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2018-07-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/34817
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spelling doaj-3a0841f8262342f6a9a58e46dfcb7a422021-05-05T16:01:43ZengeLife Sciences Publications LtdeLife2050-084X2018-07-01710.7554/eLife.34817Regenerating hair cells in vestibular sensory epithelia from humansRuth Rebecca Taylor0https://orcid.org/0000-0001-7359-1604Anastasia Filia1Ursula Paredes2Yukako Asai3Jeffrey R Holt4Michael Lovett5Andrew Forge6https://orcid.org/0000-0002-0995-0219UCL Ear Institute, University College London, London, United KingdomNational Heart and Lung Institute, Imperial College London, London, United KingdomUCL Ear Institute, University College London, London, United KingdomF.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, United StatesF.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, United StatesNational Heart and Lung Institute, Imperial College London, London, United KingdomUCL Ear Institute, University College London, London, United KingdomHuman 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.https://elifesciences.org/articles/34817hair cellsregenerationvestibulartranscriptomics
collection DOAJ
language English
format Article
sources DOAJ
author Ruth Rebecca Taylor
Anastasia Filia
Ursula Paredes
Yukako Asai
Jeffrey R Holt
Michael Lovett
Andrew Forge
spellingShingle Ruth Rebecca Taylor
Anastasia Filia
Ursula Paredes
Yukako Asai
Jeffrey R Holt
Michael Lovett
Andrew Forge
Regenerating hair cells in vestibular sensory epithelia from humans
eLife
hair cells
regeneration
vestibular
transcriptomics
author_facet Ruth Rebecca Taylor
Anastasia Filia
Ursula Paredes
Yukako Asai
Jeffrey R Holt
Michael Lovett
Andrew Forge
author_sort Ruth Rebecca Taylor
title Regenerating hair cells in vestibular sensory epithelia from humans
title_short Regenerating hair cells in vestibular sensory epithelia from humans
title_full Regenerating hair cells in vestibular sensory epithelia from humans
title_fullStr Regenerating hair cells in vestibular sensory epithelia from humans
title_full_unstemmed Regenerating hair cells in vestibular sensory epithelia from humans
title_sort regenerating hair cells in vestibular sensory epithelia from humans
publisher eLife Sciences Publications Ltd
series eLife
issn 2050-084X
publishDate 2018-07-01
description 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.
topic hair cells
regeneration
vestibular
transcriptomics
url https://elifesciences.org/articles/34817
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AT anastasiafilia regeneratinghaircellsinvestibularsensoryepitheliafromhumans
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AT yukakoasai regeneratinghaircellsinvestibularsensoryepitheliafromhumans
AT jeffreyrholt regeneratinghaircellsinvestibularsensoryepitheliafromhumans
AT michaellovett regeneratinghaircellsinvestibularsensoryepitheliafromhumans
AT andrewforge regeneratinghaircellsinvestibularsensoryepitheliafromhumans
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