Selective ablation of inner hair cells and subsequent in-situ hair cell regeneration in the neonatal mouse cochlea.


Journal

Hearing research
ISSN: 1878-5891
Titre abrégé: Hear Res
Pays: Netherlands
ID NLM: 7900445

Informations de publication

Date de publication:
08 2021
Historique:
received: 08 10 2020
revised: 24 04 2021
accepted: 10 05 2021
pubmed: 6 6 2021
medline: 8 2 2022
entrez: 5 6 2021
Statut: ppublish

Résumé

Loss of hair cells (HCs) accounts for most sensorineural hearing loss, and regeneration of cochlear HCs is considered as the ultimate strategy for restoring hearing. Several lines of evidence have shown that Lgr5+ progenitor cells can spontaneously regenerate new HCs after HC loss at the neonatal stage, and most of which are immature. IHCs are resistant to ototoxic drugs and noise and cannot be ablated efficiently in order to precisely investigate IHC regeneration in existing hearing injury models, and thus we generated a new transgenic mouse model by inserting diphtheria toxin receptor (DTR) under the control of the Vglut3 promoter. In this model, IHCs were selectively ablated in a dose-dependent manner after the injection of diphtheria toxin (DT) at the neonatal stage, while OHCs remained intact with normal hair bundle structures until adulthood. With this IHC-specific injury model, we observed HC regeneration from Lgr5+ progenitors after IHC ablation at the neonatal stage. Some of the newly generated HCs replaced the lost IHCs in-situ and re-build the structure of the organ of Corti through the asymmetrical mitosis of progenitor cells. While, the majority of the regenerated HCs did not survive until adulthood, and the loss of spiral ganglion neurons was observed after the IHC ablation, which led to profound hearing loss after DT injection in Vglut3

Identifiants

pubmed: 34089989
pii: S0378-5955(21)00109-X
doi: 10.1016/j.heares.2021.108275
pii:
doi:

Substances chimiques

Diphtheria Toxin 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

108275

Informations de copyright

Copyright © 2021. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare no competing interests.

Auteurs

Mingyu Xia (M)

Department of the Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, ENT Institute and Otorhinolaryngology, Fudan University, Room 613, Building 9, No. 83, Fenyang Road, Shanghai 200031, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

Mingxuan Wu (M)

Department of the Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, ENT Institute and Otorhinolaryngology, Fudan University, Room 613, Building 9, No. 83, Fenyang Road, Shanghai 200031, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

Liping Zhao (L)

Department of the Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, ENT Institute and Otorhinolaryngology, Fudan University, Room 613, Building 9, No. 83, Fenyang Road, Shanghai 200031, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

Jiaoyao Ma (J)

Department of the Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, ENT Institute and Otorhinolaryngology, Fudan University, Room 613, Building 9, No. 83, Fenyang Road, Shanghai 200031, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

Wenyan Li (W)

Department of the Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, ENT Institute and Otorhinolaryngology, Fudan University, Room 613, Building 9, No. 83, Fenyang Road, Shanghai 200031, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. Electronic address: wenyan_li2000@126.com.

Huawei Li (H)

Department of the Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, ENT Institute and Otorhinolaryngology, Fudan University, Room 613, Building 9, No. 83, Fenyang Road, Shanghai 200031, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai 200031, China; Shanghai Engineering Research Centre of Cochlear Implant, Shanghai 200031, China; The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China. Electronic address: hwli@shmu.edu.cn.

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