A cell-type-specific atlas of the inner ear transcriptional response to acoustic trauma.
ATF
IRF7
RiboTag
STAT3
cochlea
noise-induced hearing loss
scRNA-seq
spiral ganglion
transcriptomics
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
28 09 2021
28 09 2021
Historique:
received:
23
04
2021
revised:
29
07
2021
accepted:
03
09
2021
entrez:
30
9
2021
pubmed:
1
10
2021
medline:
11
2
2022
Statut:
ppublish
Résumé
Noise-induced hearing loss (NIHL) results from a complex interplay of damage to the sensory cells of the inner ear, dysfunction of its lateral wall, axonal retraction of type 1C spiral ganglion neurons, and activation of the immune response. We use RiboTag and single-cell RNA sequencing to survey the cell-type-specific molecular landscape of the mouse inner ear before and after noise trauma. We identify induction of the transcription factors STAT3 and IRF7 and immune-related genes across all cell-types. Yet, cell-type-specific transcriptomic changes dominate the response. The ATF3/ATF4 stress-response pathway is robustly induced in the type 1A noise-resilient neurons, potassium transport genes are downregulated in the lateral wall, mRNA metabolism genes are downregulated in outer hair cells, and deafness-associated genes are downregulated in most cell types. This transcriptomic resource is available via the Gene Expression Analysis Resource (gEAR; https://umgear.org/NIHL) and provides a blueprint for the rational development of drugs to prevent and treat NIHL.
Identifiants
pubmed: 34592158
pii: S2211-1247(21)01212-2
doi: 10.1016/j.celrep.2021.109758
pmc: PMC8709734
mid: NIHMS1744539
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
109758Subventions
Organisme : NIDCD NIH HHS
ID : R01 DC003544
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC013817
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC019370
Pays : United States
Organisme : NIDCD NIH HHS
ID : U01 DC013817
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests K.S.S., J.B.S., G.P., A.T.P., and J.B. are employees of Decibel Therapeutics. The data presented in this manuscript are registered for pending U.S. Provisional Patent Application, number: 63/151,249, title: “System and Methods for Cell Type-Specific Atlas for the Inner Ear Transcriptional Response to Acoustic Trauma,” and UMB docket number: RH-2021-073.
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