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Modulation of Wnt Signaling Enhances Inner Ear Organoid Development in 3D Culture
Stem cell-derived inner ear sensory epithelia are a promising source of tissues for treating patients with hearing loss and dizziness. We recently demonstrated how to generate inner ear sensory epithelia, designated as inner ear organoids, from mouse embryonic stem cells (ESCs) in a self-organizing...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015985/ https://www.ncbi.nlm.nih.gov/pubmed/27607106 http://dx.doi.org/10.1371/journal.pone.0162508 |
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author | DeJonge, Rachel E. Liu, Xiao-Ping Deig, Christopher R. Heller, Stefan Koehler, Karl R. Hashino, Eri |
author_facet | DeJonge, Rachel E. Liu, Xiao-Ping Deig, Christopher R. Heller, Stefan Koehler, Karl R. Hashino, Eri |
author_sort | DeJonge, Rachel E. |
collection | PubMed |
description | Stem cell-derived inner ear sensory epithelia are a promising source of tissues for treating patients with hearing loss and dizziness. We recently demonstrated how to generate inner ear sensory epithelia, designated as inner ear organoids, from mouse embryonic stem cells (ESCs) in a self-organizing 3D culture. Here we improve the efficiency of this culture system by elucidating how Wnt signaling activity can drive the induction of otic tissue. We found that a carefully timed treatment with the potent Wnt agonist CHIR99021 promotes induction of otic vesicles—a process that was previously self-organized by unknown mechanisms. The resulting otic-like vesicles have a larger lumen size and contain a greater number of Pax8/Pax2-positive otic progenitor cells than organoids derived without the Wnt agonist. Additionally, these otic-like vesicles give rise to large inner ear organoids with hair cells whose morphological, biochemical and functional properties are indistinguishable from those of vestibular hair cells in the postnatal mouse inner ear. We conclude that Wnt signaling plays a similar role during inner ear organoid formation as it does during inner ear development in the embryo. |
format | Online Article Text |
id | pubmed-5015985 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-50159852016-09-27 Modulation of Wnt Signaling Enhances Inner Ear Organoid Development in 3D Culture DeJonge, Rachel E. Liu, Xiao-Ping Deig, Christopher R. Heller, Stefan Koehler, Karl R. Hashino, Eri PLoS One Research Article Stem cell-derived inner ear sensory epithelia are a promising source of tissues for treating patients with hearing loss and dizziness. We recently demonstrated how to generate inner ear sensory epithelia, designated as inner ear organoids, from mouse embryonic stem cells (ESCs) in a self-organizing 3D culture. Here we improve the efficiency of this culture system by elucidating how Wnt signaling activity can drive the induction of otic tissue. We found that a carefully timed treatment with the potent Wnt agonist CHIR99021 promotes induction of otic vesicles—a process that was previously self-organized by unknown mechanisms. The resulting otic-like vesicles have a larger lumen size and contain a greater number of Pax8/Pax2-positive otic progenitor cells than organoids derived without the Wnt agonist. Additionally, these otic-like vesicles give rise to large inner ear organoids with hair cells whose morphological, biochemical and functional properties are indistinguishable from those of vestibular hair cells in the postnatal mouse inner ear. We conclude that Wnt signaling plays a similar role during inner ear organoid formation as it does during inner ear development in the embryo. Public Library of Science 2016-09-08 /pmc/articles/PMC5015985/ /pubmed/27607106 http://dx.doi.org/10.1371/journal.pone.0162508 Text en © 2016 DeJonge et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article DeJonge, Rachel E. Liu, Xiao-Ping Deig, Christopher R. Heller, Stefan Koehler, Karl R. Hashino, Eri Modulation of Wnt Signaling Enhances Inner Ear Organoid Development in 3D Culture |
title | Modulation of Wnt Signaling Enhances Inner Ear Organoid Development in 3D Culture |
title_full | Modulation of Wnt Signaling Enhances Inner Ear Organoid Development in 3D Culture |
title_fullStr | Modulation of Wnt Signaling Enhances Inner Ear Organoid Development in 3D Culture |
title_full_unstemmed | Modulation of Wnt Signaling Enhances Inner Ear Organoid Development in 3D Culture |
title_short | Modulation of Wnt Signaling Enhances Inner Ear Organoid Development in 3D Culture |
title_sort | modulation of wnt signaling enhances inner ear organoid development in 3d culture |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015985/ https://www.ncbi.nlm.nih.gov/pubmed/27607106 http://dx.doi.org/10.1371/journal.pone.0162508 |
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