Generating high-fidelity cochlear organoids from human pluripotent stem cells
Copyright © 2023 Elsevier Inc. All rights reserved..
Mechanosensitive hair cells in the cochlea are responsible for hearing but are vulnerable to damage by genetic mutations and environmental insults. The paucity of human cochlear tissues makes it difficult to study cochlear hair cells. Organoids offer a compelling platform to study scarce tissues in vitro; however, derivation of cochlear cell types has proven non-trivial. Here, using 3D cultures of human pluripotent stem cells, we sought to replicate key differentiation cues of cochlear specification. We found that timed modulations of Sonic Hedgehog and WNT signaling promote ventral gene expression in otic progenitors. Ventralized otic progenitors subsequently give rise to elaborately patterned epithelia containing hair cells with morphology, marker expression, and functional properties consistent with both outer and inner hair cells in the cochlea. These results suggest that early morphogenic cues are sufficient to drive cochlear induction and establish an unprecedented system to model the human auditory organ.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Cell stem cell - 30(2023), 7 vom: 06. Juli, Seite 950-961.e7 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Moore, Stephen T [VerfasserIn] |
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| Links: |
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| Themen: |
Auditory |
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| Anmerkungen: |
Date Completed 10.07.2023 Date Revised 22.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1016/j.stem.2023.06.006 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Mechanosensitive hair cells in the cochlea are responsible for hearing but are vulnerable to damage by genetic mutations and environmental insults. The paucity of human cochlear tissues makes it difficult to study cochlear hair cells. Organoids offer a compelling platform to study scarce tissues in vitro; however, derivation of cochlear cell types has proven non-trivial. Here, using 3D cultures of human pluripotent stem cells, we sought to replicate key differentiation cues of cochlear specification. We found that timed modulations of Sonic Hedgehog and WNT signaling promote ventral gene expression in otic progenitors. Ventralized otic progenitors subsequently give rise to elaborately patterned epithelia containing hair cells with morphology, marker expression, and functional properties consistent with both outer and inner hair cells in the cochlea. These results suggest that early morphogenic cues are sufficient to drive cochlear induction and establish an unprecedented system to model the human auditory organ | ||
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| 700 | 1 | |a Frolenkov, Gregory I |e verfasserin |4 aut | |
| 700 | 1 | |a Chuva de Sousa Lopes, Susana M |e verfasserin |4 aut | |
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