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Generation of inner ear organoids with functional hair cells from human pluripotent stem cells

Human inner ear tissue derived from pluripotent stem cells could provide a powerful platform for drug discovery or a source of sound- or motion-sensing cells for patients with hearing loss or balance dysfunction. Here we report a method for differentiating human pluripotent stem cells to inner ear o...

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Detalles Bibliográficos
Autores principales: Koehler, Karl R., Nie, Jing, Longworth-Mills, Emma, Liu, Xiao-Ping, Lee, Jiyoon, Holt, Jeffrey R., Hashino, Eri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462862/
https://www.ncbi.nlm.nih.gov/pubmed/28459451
http://dx.doi.org/10.1038/nbt.3840
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author Koehler, Karl R.
Nie, Jing
Longworth-Mills, Emma
Liu, Xiao-Ping
Lee, Jiyoon
Holt, Jeffrey R.
Hashino, Eri
author_facet Koehler, Karl R.
Nie, Jing
Longworth-Mills, Emma
Liu, Xiao-Ping
Lee, Jiyoon
Holt, Jeffrey R.
Hashino, Eri
author_sort Koehler, Karl R.
collection PubMed
description Human inner ear tissue derived from pluripotent stem cells could provide a powerful platform for drug discovery or a source of sound- or motion-sensing cells for patients with hearing loss or balance dysfunction. Here we report a method for differentiating human pluripotent stem cells to inner ear organoids that harbor functional hair cells. Using a three-dimensional culture system, we modulate TGF, BMP, FGF, and Wnt signaling to generate multiple otic vesicle–like structures from a single stem-cell aggregate. Over two months, the vesicles develop into inner ear organoids with sensory epithelia that are innervated by sensory neurons. Additionally, using CRISPR/Cas9, we generate an ATOH1-2A-eGFP cell line to detect hair cell induction and demonstrate that derived hair cells exhibit electrophysiological properties similar to those of native sensory hair cells. Our culture system will be useful for elucidating mechanisms of human inner ear development and testing potential inner ear therapies.
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spelling pubmed-54628622017-11-01 Generation of inner ear organoids with functional hair cells from human pluripotent stem cells Koehler, Karl R. Nie, Jing Longworth-Mills, Emma Liu, Xiao-Ping Lee, Jiyoon Holt, Jeffrey R. Hashino, Eri Nat Biotechnol Article Human inner ear tissue derived from pluripotent stem cells could provide a powerful platform for drug discovery or a source of sound- or motion-sensing cells for patients with hearing loss or balance dysfunction. Here we report a method for differentiating human pluripotent stem cells to inner ear organoids that harbor functional hair cells. Using a three-dimensional culture system, we modulate TGF, BMP, FGF, and Wnt signaling to generate multiple otic vesicle–like structures from a single stem-cell aggregate. Over two months, the vesicles develop into inner ear organoids with sensory epithelia that are innervated by sensory neurons. Additionally, using CRISPR/Cas9, we generate an ATOH1-2A-eGFP cell line to detect hair cell induction and demonstrate that derived hair cells exhibit electrophysiological properties similar to those of native sensory hair cells. Our culture system will be useful for elucidating mechanisms of human inner ear development and testing potential inner ear therapies. 2017-05-01 2017-06 /pmc/articles/PMC5462862/ /pubmed/28459451 http://dx.doi.org/10.1038/nbt.3840 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Koehler, Karl R.
Nie, Jing
Longworth-Mills, Emma
Liu, Xiao-Ping
Lee, Jiyoon
Holt, Jeffrey R.
Hashino, Eri
Generation of inner ear organoids with functional hair cells from human pluripotent stem cells
title Generation of inner ear organoids with functional hair cells from human pluripotent stem cells
title_full Generation of inner ear organoids with functional hair cells from human pluripotent stem cells
title_fullStr Generation of inner ear organoids with functional hair cells from human pluripotent stem cells
title_full_unstemmed Generation of inner ear organoids with functional hair cells from human pluripotent stem cells
title_short Generation of inner ear organoids with functional hair cells from human pluripotent stem cells
title_sort generation of inner ear organoids with functional hair cells from human pluripotent stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462862/
https://www.ncbi.nlm.nih.gov/pubmed/28459451
http://dx.doi.org/10.1038/nbt.3840
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