Greater epithelial ridge cells are the principal organoid-forming progenitors of the mouse cochlea.

auditory periphery epigenetic reprogramming hair cell regeneration inner ear organoid otic supporting cell

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
19 01 2021
Historique:
received: 14 08 2020
revised: 01 11 2020
accepted: 21 12 2020
entrez: 20 1 2021
pubmed: 21 1 2021
medline: 29 1 2022
Statut: ppublish

Résumé

In mammals, hearing loss is irreversible due to the lack of regenerative potential of non-sensory cochlear cells. Neonatal cochlear cells, however, can grow into organoids that harbor sensory epithelial cells, including hair cells and supporting cells. Here, we purify different cochlear cell types from neonatal mice, validate the composition of the different groups with single-cell RNA sequencing (RNA-seq), and assess the various groups' potential to grow into inner ear organoids. We find that the greater epithelial ridge (GER), a transient cell population that disappears during post-natal cochlear maturation, harbors the most potent organoid-forming cells. We identified three distinct GER cell groups that correlate with a specific spatial distribution of marker genes. Organoid formation was synergistically enhanced when the cells were cultured at increasing density. This effect is not due to diffusible signals but requires direct cell-to-cell contact. Our findings improve the development of cell-based assays to study culture-generated inner ear cell types.

Identifiants

pubmed: 33472062
pii: S2211-1247(20)31635-1
doi: 10.1016/j.celrep.2020.108646
pmc: PMC7847202
mid: NIHMS1664961
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

108646

Subventions

Organisme : NIDCD NIH HHS
ID : P30 DC010363
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC015201
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC017689
Pays : United States
Organisme : NIDCD NIH HHS
ID : T32 DC015209
Pays : United States

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests S.H. is a paid consultant of Pipeline Therapeutics.

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Auteurs

Marie Kubota (M)

Department of Otolaryngology - Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: kubomari@stanford.edu.

Mirko Scheibinger (M)

Department of Otolaryngology - Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

Taha A Jan (TA)

Department of Otolaryngology - Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Otolaryngology - Head & Neck Surgery, University of California San Francisco, San Francisco, CA 94115, USA.

Stefan Heller (S)

Department of Otolaryngology - Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: hellers@stanford.edu.

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