Yap-lin28a axis targets let7-Wnt pathway to restore progenitors for initiating regeneration

  1. Zhian Ye
  2. Zhongwu Su
  3. Siyu Xie
  4. Yuye Liu
  5. Yongqiang Wang
  6. Xi Xu
  7. Yiqing Zheng
  8. Meng Zhao  Is a corresponding author
  9. Linjia Jiang  Is a corresponding author
  1. Sun Yat-Sen Memorial Hospital, China
  2. Sun Yat-Sen University, China

Abstract

The sox2 expressing (sox2+) progenitors in adult mammalian inner ear lose the capacity to regenerate while progenitors in the zebrafish lateral line are able to proliferate and regenerate damaged HCs throughout lifetime. To mimic the HC damage in mammals we have established a zebrafish severe injury model to eliminate both progenitors and HCs. The atoh1a expressing (atoh1a+) HC precursors were the main population that survived post severe injury, and gained sox2 expression to initiate progenitor regeneration. In response to severe injury, yap was activated to upregulate lin28a transcription. Severe-injury-induced progenitor regeneration was disabled in lin28a or yap mutants. In contrary, overexpression of lin28a initiated the recovery of sox2+ progenitors. Mechanistically, microRNA let7 acted downstream of lin28a to activate Wnt pathway for promoting regeneration. Our findings that lin28a is necessary and sufficient to regenerate the exhausted sox2+ progenitors shed light on restoration of progenitors to initiate HC regeneration in mammals.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Zhian Ye

    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Zhongwu Su

    Department of Otolaryngology, Sun Yat-Sen Memorial Hospital, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Siyu Xie

    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Yuye Liu

    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Yongqiang Wang

    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Xi Xu

    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Yiqing Zheng

    Department of Otolaryngology, Sun Yat-Sen Memorial Hospital, Guangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Meng Zhao

    Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China
    For correspondence
    zhaom38@mail.sysu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
  9. Linjia Jiang

    Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Guangzhou, China
    For correspondence
    jianglj7@mail.sysu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8854-2610

Funding

Ministry of Science and Technology of the People's Republic of China (National Key R&D Program of China,2018YFA0108304)

  • Linjia Jiang

National Science Foundation (Youth Project,81800164)

  • Linjia Jiang

National Science Foundation (General Project,31871467)

  • Linjia Jiang

Guangdong Science and Technology Department (basic research project FF0C;2018A030313497)

  • Linjia Jiang

Guangdong Science and Technology Department (The key Research and Development Program of Guangdong Province,2019B020234002)

  • Meng Zhao

Shenzhen Foundation of Science and Technology (JCYJ20170818103626421)

  • Meng Zhao

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Tanya T Whitfield, University of Sheffield, United Kingdom

Publication history

  1. Received: February 5, 2020
  2. Accepted: April 29, 2020
  3. Accepted Manuscript published: April 30, 2020 (version 1)
  4. Version of Record published: May 26, 2020 (version 2)

Copyright

© 2020, Ye 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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  1. Zhian Ye
  2. Zhongwu Su
  3. Siyu Xie
  4. Yuye Liu
  5. Yongqiang Wang
  6. Xi Xu
  7. Yiqing Zheng
  8. Meng Zhao
  9. Linjia Jiang
(2020)
Yap-lin28a axis targets let7-Wnt pathway to restore progenitors for initiating regeneration
eLife 9:e55771.
https://doi.org/10.7554/eLife.55771

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