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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2017
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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. |
format | Online Article Text |
id | pubmed-5462862 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
record_format | MEDLINE/PubMed |
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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