Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1
- Baylor College of Medicine, United States
- University of Southern California, United States
Abstract
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 improved 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.
Data availability
Sequencing data have been deposited in GEO under accession codes GSE122732 and GSE121610
-
RNA-seq of adult utricle supporting cellsNCBI Gene Expression Omnibus, GSE122732.
-
ATAC-seq of adult utricle supporting cellsNCBI Gene Expression Omnibus, GSE121610.
Article and author information
Author details
Funding
National Cancer Institute (CA125123)
- Andrew K Groves
Vivian L Smith Foundation and MacDonald Research Fund Award (16RDM001)
- James F Martin
Transatlantic Network of Excellence Award LeDucq Foundation Transatlantic Networks of Excellence in Cardiovascular Research (14CVD01)
- James F Martin
National Institute on Deafness and Other Communication Disorders (RO1DC014832)
- Andrew K Groves
National Institute on Deafness and Other Communication Disorders (RO1DC015829)
- Neil Segil
Eunice Kennedy Shriver National Institute of Child Health and Human Development (RO1DE023177)
- James F Martin
National Heart, Lung, and Blood Institute (RO1HL127717)
- James F Martin
National Heart, Lung, and Blood Institute (RO1HL130804)
- James F Martin
National Heart, Lung, and Blood Institute (RO1HL118761)
- James F Martin
National Institutes of Health (DP2EB020399)
- Chenghang Zong
National Heart, Lung, and Blood Institute (F31HL136065)
- Matthew C Hill
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (AN-4956) of Baylor College of Medicine
Reviewing Editor
- Francois Guillemot, The Francis Crick Institute, United Kingdom
Publication history
- Received: December 12, 2018
- Accepted: April 28, 2019
- Accepted Manuscript published: April 29, 2019 (version 1)
- Version of Record published: May 7, 2019 (version 2)
Copyright
© 2019, Jen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 4,655
- Page views
-
- 657
- Downloads
-
- 31
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1
eLife 8:e44328.
https://doi.org/10.7554/eLife.44328
