Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1.
Animals
Basic Helix-Loop-Helix Transcription Factors
/ genetics
Cell Cycle
Cell Death
Cochlea
Epigenesis, Genetic
Female
Gene Expression Regulation
Hair Cells, Auditory
/ metabolism
Male
Mice
Regeneration
/ physiology
Saccule and Utricle
/ metabolism
Transcription Factors
Transcriptome
Transduction, Genetic
RNA-seq
cochlea
developmental biology
hair cell
mouse
neuroscience
regeneration
vestibular
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
29 04 2019
29 04 2019
Historique:
received:
12
12
2018
accepted:
28
04
2019
pubmed:
30
4
2019
medline:
27
2
2020
entrez:
30
4
2019
Statut:
epublish
Résumé
The mammalian cochlea loses its ability to regenerate new hair cells prior to the onset of hearing. In contrast, the adult vestibular system can produce new hair cells in response to damage, or by reprogramming of supporting cells with the hair cell transcription factor Atoh1. We used RNA-seq and ATAC-seq to probe the transcriptional and epigenetic responses of utricle supporting cells to damage and Atoh1 transduction. We show that the regenerative response of the utricle correlates with a more accessible chromatin structure in utricle supporting cells compared to their cochlear counterparts. We also provide evidence that Atoh1 transduction of supporting cells is able to promote increased transcriptional accessibility of some hair cell genes. Our study offers a possible explanation for regenerative differences between sensory organs of the inner ear, but shows that additional factors to Atoh1 may be required for optimal reprogramming of hair cell fate.
Identifiants
pubmed: 31033441
doi: 10.7554/eLife.44328
pii: 44328
pmc: PMC6504235
doi:
pii:
Substances chimiques
Atoh1 protein, mouse
0
Basic Helix-Loop-Helix Transcription Factors
0
Transcription Factors
0
Banques de données
GEO
['GSE122732', 'GSE121610']
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
Subventions
Organisme : NIDCD NIH HHS
ID : RO1DC015829
Pays : United States
Organisme : MacDonald Research Fund
ID : 16RDM001
Pays : International
Organisme : Fondation Leducq
ID : Transatlantic Network of Excellence Award (14CVD01)
Pays : International
Organisme : NHLBI NIH HHS
ID : RO1HL118761
Pays : United States
Organisme : NHLBI NIH HHS
ID : RO1HL127717
Pays : United States
Organisme : NIH HHS
ID : DP2EB020399
Pays : United States
Organisme : NIDCD NIH HHS
ID : RO1DC014832
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC014832
Pays : United States
Organisme : NCI NIH HHS
ID : CA125123
Pays : United States
Organisme : Eunice Kennedy Shriver National Institute of Child Health and Human Development
ID : RO1DE023177
Pays : International
Organisme : NIDCD NIH HHS
ID : R01 DC015829
Pays : United States
Organisme : NIDCD NIH HHS
ID : T32 DC009975
Pays : United States
Organisme : NHLBI NIH HHS
ID : F31HL136065
Pays : United States
Organisme : Hearing Health Foundation
ID : Hearing Restoration Project Consortium Grant
Pays : International
Organisme : Transatlantic Network of Excellence Award LeDucq Foundation Transatlantic Networks of Excellence in Cardiovascular Research
ID : 14CVD01
Pays : International
Organisme : NHLBI NIH HHS
ID : RO1HL130804
Pays : United States
Informations de copyright
© 2019, Jen et al.
Déclaration de conflit d'intérêts
HJ, MH, LT, KS, WC, HZ, HY, JL, CZ, JM, NS, AG No competing interests declared
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