Loss of Mst1/2 activity promotes non-mitotic hair cell generation in the neonatal organ of Corti
Abstract Mammalian sensory hair cells (HCs) have limited capacity for regeneration, which leads to permanent hearing loss after HC death. Here, we used in vitro RNA-sequencing to show that the Hippo signaling pathway is involved in HC damage and self-repair processes. Turning off Hippo signaling thr...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-10-01
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| Series: | npj Regenerative Medicine |
| Online Access: | https://doi.org/10.1038/s41536-022-00261-4 |
| _version_ | 1797991760038723584 |
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| author | Xiaoling Lu Huiqian Yu Jiaoyao Ma Kunkun Wang Luo Guo Yanping Zhang Boan Li Zehang Zhao Huawei Li Shan Sun |
| author_facet | Xiaoling Lu Huiqian Yu Jiaoyao Ma Kunkun Wang Luo Guo Yanping Zhang Boan Li Zehang Zhao Huawei Li Shan Sun |
| author_sort | Xiaoling Lu |
| collection | DOAJ |
| description | Abstract Mammalian sensory hair cells (HCs) have limited capacity for regeneration, which leads to permanent hearing loss after HC death. Here, we used in vitro RNA-sequencing to show that the Hippo signaling pathway is involved in HC damage and self-repair processes. Turning off Hippo signaling through Mst1/2 inhibition or Yap overexpression induces YAP nuclear accumulation, especially in supporting cells, which induces supernumerary HC production and HC regeneration after injury. Mechanistically, these effects of Hippo signaling work synergistically with the Notch pathway. Importantly, the supernumerary HCs not only express HC markers, but also have cilia structures that are able to form neural connections to auditory regions in vivo. Taken together, regulating Hippo suggests new strategies for promoting cochlear supporting cell proliferation, HC regeneration, and reconnection with neurons in mammals. |
| first_indexed | 2024-04-11T08:57:24Z |
| format | Article |
| id | doaj.art-861a0c7295b449579d604e0fa8535a2c |
| institution | Directory Open Access Journal |
| issn | 2057-3995 |
| language | English |
| last_indexed | 2024-04-11T08:57:24Z |
| publishDate | 2022-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Regenerative Medicine |
| spelling | doaj.art-861a0c7295b449579d604e0fa8535a2c2022-12-22T04:33:09ZengNature Portfolionpj Regenerative Medicine2057-39952022-10-017111310.1038/s41536-022-00261-4Loss of Mst1/2 activity promotes non-mitotic hair cell generation in the neonatal organ of CortiXiaoling Lu0Huiqian Yu1Jiaoyao Ma2Kunkun Wang3Luo Guo4Yanping Zhang5Boan Li6Zehang Zhao7Huawei Li8Shan Sun9ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine (Fudan University), Fudan UniversityENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine (Fudan University), Fudan UniversityENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine (Fudan University), Fudan UniversityENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine (Fudan University), Fudan UniversityENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine (Fudan University), Fudan UniversityENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine (Fudan University), Fudan UniversityXiamen University School of Life SciencesXiamen University School of Life SciencesENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine (Fudan University), Fudan UniversityENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, NHC Key Laboratory of Hearing Medicine (Fudan University), Fudan UniversityAbstract Mammalian sensory hair cells (HCs) have limited capacity for regeneration, which leads to permanent hearing loss after HC death. Here, we used in vitro RNA-sequencing to show that the Hippo signaling pathway is involved in HC damage and self-repair processes. Turning off Hippo signaling through Mst1/2 inhibition or Yap overexpression induces YAP nuclear accumulation, especially in supporting cells, which induces supernumerary HC production and HC regeneration after injury. Mechanistically, these effects of Hippo signaling work synergistically with the Notch pathway. Importantly, the supernumerary HCs not only express HC markers, but also have cilia structures that are able to form neural connections to auditory regions in vivo. Taken together, regulating Hippo suggests new strategies for promoting cochlear supporting cell proliferation, HC regeneration, and reconnection with neurons in mammals.https://doi.org/10.1038/s41536-022-00261-4 |
| spellingShingle | Xiaoling Lu Huiqian Yu Jiaoyao Ma Kunkun Wang Luo Guo Yanping Zhang Boan Li Zehang Zhao Huawei Li Shan Sun Loss of Mst1/2 activity promotes non-mitotic hair cell generation in the neonatal organ of Corti npj Regenerative Medicine |
| title | Loss of Mst1/2 activity promotes non-mitotic hair cell generation in the neonatal organ of Corti |
| title_full | Loss of Mst1/2 activity promotes non-mitotic hair cell generation in the neonatal organ of Corti |
| title_fullStr | Loss of Mst1/2 activity promotes non-mitotic hair cell generation in the neonatal organ of Corti |
| title_full_unstemmed | Loss of Mst1/2 activity promotes non-mitotic hair cell generation in the neonatal organ of Corti |
| title_short | Loss of Mst1/2 activity promotes non-mitotic hair cell generation in the neonatal organ of Corti |
| title_sort | loss of mst1 2 activity promotes non mitotic hair cell generation in the neonatal organ of corti |
| url | https://doi.org/10.1038/s41536-022-00261-4 |
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