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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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 |
work_keys_str_mv |
AT ruthrebeccataylor regeneratinghaircellsinvestibularsensoryepitheliafromhumans AT anastasiafilia regeneratinghaircellsinvestibularsensoryepitheliafromhumans AT ursulaparedes regeneratinghaircellsinvestibularsensoryepitheliafromhumans AT yukakoasai regeneratinghaircellsinvestibularsensoryepitheliafromhumans AT jeffreyrholt regeneratinghaircellsinvestibularsensoryepitheliafromhumans AT michaellovett regeneratinghaircellsinvestibularsensoryepitheliafromhumans AT andrewforge regeneratinghaircellsinvestibularsensoryepitheliafromhumans |
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1721459652658462720 |