Precise genetic control of ATOH1 enhances maturation of regenerated hair cells in the mature mouse utricle.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 Oct 2024
24 Oct 2024
Historique:
received:
25
07
2023
accepted:
27
09
2024
medline:
25
10
2024
pubmed:
25
10
2024
entrez:
25
10
2024
Statut:
epublish
Résumé
Vestibular hair cells are mechanoreceptors critical for detecting head position and motion. In mammals, hair cell loss causes vestibular dysfunction as spontaneous regeneration is nearly absent. Constitutive expression of exogenous ATOH1, a hair cell transcription factor, increases hair cell regeneration, however, these cells fail to fully mature. Here, we profiled mouse utricles at 14 time points, and defined transcriptomes of developing and mature vestibular hair cells. To mimic native hair cells which downregulate endogenous ATOH1 as they mature, we engineered viral vectors carrying the supporting cell promoters GFAP and RLBP1. In utricles damaged ex vivo, both CMV-ATOH1 and GFAP-ATOH1 increased regeneration more effectively than RLBP1-ATOH1, while GFAP-ATOH1 and RLBP1-ATOH1 induced hair cells with more mature transcriptomes. In utricles damaged in vivo, GFAP-ATOH1 induced regeneration of hair cells expressing genes indicative of maturing type II hair cells, and more hair cells with bundles and synapses than untreated organs. Together our results demonstrate the efficacy of spatiotemporal control of ATOH1 overexpression in inner ear hair cell regeneration.
Identifiants
pubmed: 39448563
doi: 10.1038/s41467-024-53153-0
pii: 10.1038/s41467-024-53153-0
doi:
Substances chimiques
Atoh1 protein, mouse
0
Basic Helix-Loop-Helix Transcription Factors
0
Glial Fibrillary Acidic Protein
0
glial fibrillary astrocytic protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9166Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD)
ID : R01DC016919
Informations de copyright
© 2024. The Author(s).
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