Generation of inner ear sensory epithelia from pluripotent stem cells in 3D culture.
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| Title: | Generation of inner ear sensory epithelia from pluripotent stem cells in 3D culture. |
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| Authors: | Koehler, Karl R., Mikosz, Andrew M., Molosh, Andrei I., Patel, Dharmeshkumar, Hashino, Eri |
| Source: | Nature. 8/8/2013, Vol. 500 Issue 7461, p217-221. 5p. 4 Graphs. |
| Subjects: | Ear, Epithelial cells, Pluripotent stem cells, Embryonic stem cells, Hair cells, Sensory neurons |
| Abstract: | The inner ear contains sensory epithelia that detect head movements, gravity and sound. It is unclear how to develop these sensory epithelia from pluripotent stem cells, a process that will be critical for modelling inner ear disorders or developing cell-based therapies for profound hearing loss and balance disorders. So far, attempts to derive inner ear mechanosensitive hair cells and sensory neurons have resulted in inefficient or incomplete phenotypic conversion of stem cells into inner-ear-like cells. A key insight lacking from these previous studies is the importance of the non-neural and preplacodal ectoderm, two critical precursors during inner ear development. Here we report the stepwise differentiation of inner ear sensory epithelia from mouse embryonic stem cells (ESCs) in three-dimensional culture. We show that by recapitulating in vivo development with precise temporal control of signalling pathways, ESC aggregates transform sequentially into non-neural, preplacodal and otic-placode-like epithelia. Notably, in a self-organized process that mimics normal development, vesicles containing prosensory cells emerge from the presumptive otic placodes and give rise to hair cells bearing stereocilia bundles and a kinocilium. Moreover, these stem-cell-derived hair cells exhibit functional properties of native mechanosensitive hair cells and form specialized synapses with sensory neurons that have also arisen from ESCs in the culture. Finally, we demonstrate how these vesicles are structurally and biochemically comparable to developing vestibular end organs. Our data thus establish a new in vitro model of inner ear differentiation that can be used to gain deeper insight into inner ear development and disorder. [ABSTRACT FROM AUTHOR] |
| Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 89596329 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Generation of inner ear sensory epithelia from pluripotent stem cells in 3D culture. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Koehler%2C+Karl+R%2E%22">Koehler, Karl R.</searchLink><br /><searchLink fieldCode="AR" term="%22Mikosz%2C+Andrew+M%2E%22">Mikosz, Andrew M.</searchLink><br /><searchLink fieldCode="AR" term="%22Molosh%2C+Andrei+I%2E%22">Molosh, Andrei I.</searchLink><br /><searchLink fieldCode="AR" term="%22Patel%2C+Dharmeshkumar%22">Patel, Dharmeshkumar</searchLink><br /><searchLink fieldCode="AR" term="%22Hashino%2C+Eri%22">Hashino, Eri</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Nature%22">Nature</searchLink>. 8/8/2013, Vol. 500 Issue 7461, p217-221. 5p. 4 Graphs. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Ear%22">Ear</searchLink><br /><searchLink fieldCode="DE" term="%22Epithelial+cells%22">Epithelial cells</searchLink><br /><searchLink fieldCode="DE" term="%22Pluripotent+stem+cells%22">Pluripotent stem cells</searchLink><br /><searchLink fieldCode="DE" term="%22Embryonic+stem+cells%22">Embryonic stem cells</searchLink><br /><searchLink fieldCode="DE" term="%22Hair+cells%22">Hair cells</searchLink><br /><searchLink fieldCode="DE" term="%22Sensory+neurons%22">Sensory neurons</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: The inner ear contains sensory epithelia that detect head movements, gravity and sound. It is unclear how to develop these sensory epithelia from pluripotent stem cells, a process that will be critical for modelling inner ear disorders or developing cell-based therapies for profound hearing loss and balance disorders. So far, attempts to derive inner ear mechanosensitive hair cells and sensory neurons have resulted in inefficient or incomplete phenotypic conversion of stem cells into inner-ear-like cells. A key insight lacking from these previous studies is the importance of the non-neural and preplacodal ectoderm, two critical precursors during inner ear development. Here we report the stepwise differentiation of inner ear sensory epithelia from mouse embryonic stem cells (ESCs) in three-dimensional culture. We show that by recapitulating in vivo development with precise temporal control of signalling pathways, ESC aggregates transform sequentially into non-neural, preplacodal and otic-placode-like epithelia. Notably, in a self-organized process that mimics normal development, vesicles containing prosensory cells emerge from the presumptive otic placodes and give rise to hair cells bearing stereocilia bundles and a kinocilium. Moreover, these stem-cell-derived hair cells exhibit functional properties of native mechanosensitive hair cells and form specialized synapses with sensory neurons that have also arisen from ESCs in the culture. Finally, we demonstrate how these vesicles are structurally and biochemically comparable to developing vestibular end organs. Our data thus establish a new in vitro model of inner ear differentiation that can be used to gain deeper insight into inner ear development and disorder. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1038/nature12298 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 5 StartPage: 217 Subjects: – SubjectFull: Ear Type: general – SubjectFull: Epithelial cells Type: general – SubjectFull: Pluripotent stem cells Type: general – SubjectFull: Embryonic stem cells Type: general – SubjectFull: Hair cells Type: general – SubjectFull: Sensory neurons Type: general Titles: – TitleFull: Generation of inner ear sensory epithelia from pluripotent stem cells in 3D culture. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Koehler, Karl R. – PersonEntity: Name: NameFull: Mikosz, Andrew M. – PersonEntity: Name: NameFull: Molosh, Andrei I. – PersonEntity: Name: NameFull: Patel, Dharmeshkumar – PersonEntity: Name: NameFull: Hashino, Eri IsPartOfRelationships: – BibEntity: Dates: – D: 08 M: 08 Text: 8/8/2013 Type: published Y: 2013 Identifiers: – Type: issn-print Value: 00280836 Numbering: – Type: volume Value: 500 – Type: issue Value: 7461 Titles: – TitleFull: Nature Type: main |
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