Applications of Lgr5-Positive Cochlear Progenitors (LCPs) to the Study of Hair Cell Differentiation
The mouse cochlea contains approximately 15,000 hair cells. Its dimensions and location, and the small number of hair cells, make mechanistic, developmental and cellular replacement studies difficult. We recently published a protocol to expand and differentiate murine neonatal cochlear progenitor ce...
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| Format: | Article |
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Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2019.00014/full |
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| author | Danielle R. Lenz Danielle R. Lenz Niliksha Gunewardene Niliksha Gunewardene Dunia E. Abdul-Aziz Dunia E. Abdul-Aziz Quan Wang Quan Wang Tyler M. Gibson Tyler M. Gibson Albert S. B. Edge Albert S. B. Edge Albert S. B. Edge |
| author_facet | Danielle R. Lenz Danielle R. Lenz Niliksha Gunewardene Niliksha Gunewardene Dunia E. Abdul-Aziz Dunia E. Abdul-Aziz Quan Wang Quan Wang Tyler M. Gibson Tyler M. Gibson Albert S. B. Edge Albert S. B. Edge Albert S. B. Edge |
| author_sort | Danielle R. Lenz |
| collection | DOAJ |
| description | The mouse cochlea contains approximately 15,000 hair cells. Its dimensions and location, and the small number of hair cells, make mechanistic, developmental and cellular replacement studies difficult. We recently published a protocol to expand and differentiate murine neonatal cochlear progenitor cells into 3D organoids that recapitulate developmental pathways and can generate large numbers of hair cells with intact stereociliary bundles, molecular markers of the native cells and mechanotransduction channel activity, as indicated by FM1-43 uptake. Here, we elaborate on the method and application of these Lgr5-positive cochlear progenitors, termed LCPs, to the study of inner ear development and differentiation. We demonstrate the use of these cells for testing several drug candidates, gene silencing and overexpression, as well as genomic modification using CRISPR/Cas9. We thus establish LCPs as a valuable in vitro tool for the analysis of progenitor cell manipulation and hair cell differentiation. |
| first_indexed | 2024-04-13T01:46:17Z |
| format | Article |
| id | doaj.art-40c086e4f97d47959e0cc5e925f4eb01 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-13T01:46:17Z |
| publishDate | 2019-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-40c086e4f97d47959e0cc5e925f4eb012022-12-22T03:08:02ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2019-02-01710.3389/fcell.2019.00014384512Applications of Lgr5-Positive Cochlear Progenitors (LCPs) to the Study of Hair Cell DifferentiationDanielle R. Lenz0Danielle R. Lenz1Niliksha Gunewardene2Niliksha Gunewardene3Dunia E. Abdul-Aziz4Dunia E. Abdul-Aziz5Quan Wang6Quan Wang7Tyler M. Gibson8Tyler M. Gibson9Albert S. B. Edge10Albert S. B. Edge11Albert S. B. Edge12Department of Otolaryngology, Harvard Medical School, Boston, MA, United StatesEaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology, Harvard Medical School, Boston, MA, United StatesEaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology, Harvard Medical School, Boston, MA, United StatesEaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology, Harvard Medical School, Boston, MA, United StatesEaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology, Harvard Medical School, Boston, MA, United StatesEaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology, Harvard Medical School, Boston, MA, United StatesEaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA, United StatesHarvard Stem Cell Institute, Cambridge, MA, United StatesThe mouse cochlea contains approximately 15,000 hair cells. Its dimensions and location, and the small number of hair cells, make mechanistic, developmental and cellular replacement studies difficult. We recently published a protocol to expand and differentiate murine neonatal cochlear progenitor cells into 3D organoids that recapitulate developmental pathways and can generate large numbers of hair cells with intact stereociliary bundles, molecular markers of the native cells and mechanotransduction channel activity, as indicated by FM1-43 uptake. Here, we elaborate on the method and application of these Lgr5-positive cochlear progenitors, termed LCPs, to the study of inner ear development and differentiation. We demonstrate the use of these cells for testing several drug candidates, gene silencing and overexpression, as well as genomic modification using CRISPR/Cas9. We thus establish LCPs as a valuable in vitro tool for the analysis of progenitor cell manipulation and hair cell differentiation.https://www.frontiersin.org/article/10.3389/fcell.2019.00014/fullLgr5differentiationproliferationhair cellssupporting cellscochlea |
| spellingShingle | Danielle R. Lenz Danielle R. Lenz Niliksha Gunewardene Niliksha Gunewardene Dunia E. Abdul-Aziz Dunia E. Abdul-Aziz Quan Wang Quan Wang Tyler M. Gibson Tyler M. Gibson Albert S. B. Edge Albert S. B. Edge Albert S. B. Edge Applications of Lgr5-Positive Cochlear Progenitors (LCPs) to the Study of Hair Cell Differentiation Frontiers in Cell and Developmental Biology Lgr5 differentiation proliferation hair cells supporting cells cochlea |
| title | Applications of Lgr5-Positive Cochlear Progenitors (LCPs) to the Study of Hair Cell Differentiation |
| title_full | Applications of Lgr5-Positive Cochlear Progenitors (LCPs) to the Study of Hair Cell Differentiation |
| title_fullStr | Applications of Lgr5-Positive Cochlear Progenitors (LCPs) to the Study of Hair Cell Differentiation |
| title_full_unstemmed | Applications of Lgr5-Positive Cochlear Progenitors (LCPs) to the Study of Hair Cell Differentiation |
| title_short | Applications of Lgr5-Positive Cochlear Progenitors (LCPs) to the Study of Hair Cell Differentiation |
| title_sort | applications of lgr5 positive cochlear progenitors lcps to the study of hair cell differentiation |
| topic | Lgr5 differentiation proliferation hair cells supporting cells cochlea |
| url | https://www.frontiersin.org/article/10.3389/fcell.2019.00014/full |
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