Tags

Type your tag names separated by a space and hit enter

Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1.

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 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.

Links

  • PMC Free PDF
  • PMC Free Full Text
  • FREE Publisher Full Text
  • Authors+Show Affiliations

    ,

    Program in Developmental Biology, Baylor College of Medicine, Houston, United States.

    ,

    Program in Developmental Biology, Baylor College of Medicine, Houston, United States.

    ,

    Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, United States. Caruso Department of Otolaryngology - Head and Neck Surgery, Keck School of Medicine, University of Southern California, Los Angeles, United States.

    ,

    Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, United States.

    ,

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.

    ,

    Department of Neuroscience, Baylor College of Medicine, Houston, United States.

    ,

    Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, United States. Caruso Department of Otolaryngology - Head and Neck Surgery, Keck School of Medicine, University of Southern California, Los Angeles, United States.

    ,

    Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, United States. Caruso Department of Otolaryngology - Head and Neck Surgery, Keck School of Medicine, University of Southern California, Los Angeles, United States.

    ,

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.

    ,

    Program in Developmental Biology, Baylor College of Medicine, Houston, United States. Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, United States. The Texas Heart Institute, Houston, United States.

    ,

    Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, United States. Caruso Department of Otolaryngology - Head and Neck Surgery, Keck School of Medicine, University of Southern California, Los Angeles, United States.

    Program in Developmental Biology, Baylor College of Medicine, Houston, United States. Department of Neuroscience, Baylor College of Medicine, Houston, United States.

    Source

    eLife 8: 2019 Apr 29 pg

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31033441

    Citation

    Jen, Hsin-I, et al. "Transcriptomic and Epigenetic Regulation of Hair Cell Regeneration in the Mouse Utricle and Its Potentiation By Atoh1." ELife, vol. 8, 2019.
    Jen HI, Hill MC, Tao L, et al. Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1. Elife. 2019;8.
    Jen, H. I., Hill, M. C., Tao, L., Sheng, K., Cao, W., Zhang, H., ... Groves, A. K. (2019). Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1. ELife, 8, doi:10.7554/eLife.44328.
    Jen HI, et al. Transcriptomic and Epigenetic Regulation of Hair Cell Regeneration in the Mouse Utricle and Its Potentiation By Atoh1. Elife. 2019 Apr 29;8 PubMed PMID: 31033441.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Transcriptomic and epigenetic regulation of hair cell regeneration in the mouse utricle and its potentiation by Atoh1. AU - Jen,Hsin-I, AU - Hill,Matthew C, AU - Tao,Litao, AU - Sheng,Kuanwei, AU - Cao,Wenjian, AU - Zhang,Hongyuan, AU - Yu,Haoze V, AU - Llamas,Juan, AU - Zong,Chenghang, AU - Martin,James F, AU - Segil,Neil, AU - Groves,Andrew K, Y1 - 2019/04/29/ PY - 2018/12/12/received PY - 2019/04/28/accepted PY - 2019/4/30/pubmed PY - 2019/4/30/medline PY - 2019/4/30/entrez KW - RNA-seq KW - cochlea KW - developmental biology KW - hair cell KW - mouse KW - neuroscience KW - regeneration KW - vestibular JF - eLife JO - Elife VL - 8 N2 - 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. SN - 2050-084X UR - https://www.unboundmedicine.com/medline/citation/31033441/Transcriptomic_and_epigenetic_regulation_of_hair_cell_regeneration_in_the_mouse_utricle_and_its_potentiation_by_Atoh1 L2 - https://doi.org/10.7554/eLife.44328 DB - PRIME DP - Unbound Medicine ER -