1. Developmental Biology
  2. Neuroscience
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Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1

  1. Hsin-I Jen
  2. Matthew C Hill
  3. Litao Tao
  4. Kuanwei Sheng
  5. Wenjian Cao
  6. Hongyuan Zhang
  7. Haoze V Yu
  8. Juan Llamas
  9. Chenghang Zong
  10. James F Martin
  11. Neil Segil
  12. Andrew K Groves  Is a corresponding author
  1. Baylor College of Medicine, United States
  2. University of Southern California, United States
Research Article
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Cite this article as: eLife 2019;8:e44328 doi: 10.7554/eLife.44328

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

The following data sets were generated

Article and author information

Author details

  1. Hsin-I Jen

    Program in Developmental Biology, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Matthew C Hill

    Program in Developmental Biology, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Litao Tao

    Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Kuanwei Sheng

    Program Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Wenjian Cao

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Hongyuan Zhang

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Haoze V Yu

    Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Juan Llamas

    Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Chenghang Zong

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.

  10. James F Martin

    Program in Developmental Biology, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.

  11. Neil Segil

    Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  12. Andrew K Groves

    Program in Developmental Biology, Baylor College of Medicine, Houston, United States
    For correspondence
    akgroves@bcm.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0784-7998

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

  1. Francois Guillemot, The Francis Crick Institute, United Kingdom

Publication history

  1. Received: December 12, 2018
  2. Accepted: April 28, 2019
  3. Accepted Manuscript published: April 29, 2019 (version 1)
  4. 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.

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