Renal interstitial cells promote nephron regeneration by secreting prostaglandin E2

Abstract

In organ regeneration, progenitor and stem cells reside in their native microenvironment, which provides dynamic physical and chemical cues essential to their survival, proliferation, and differentiation. However, the types of cells that form the native microenvironment for renal progenitor cells (RPCs) have not been clarified. Here, single-cell sequencing of zebrafish kidney reveals fabp10a as a principal marker of renal interstitial cells (RICs), which can be specifically labeled by GFP under the control of fabp10a promoter in the fabp10a:GFP transgenic zebrafish. During nephron regeneration, the formation of nephrons is supported by RICs that form a network to wrap the RPC aggregates. RICs that are in close contact with RPC aggregates express Cyclooxygenase 2 (Cox2) and secrete prostaglandin E2 (PGE2). Inhibiting PGE2 production prevents nephrogenesis by reducing the proliferation of RPCs. PGE2 cooperates with Wnt4a to promote nephron maturation by regulating β-catenin stability of RPC aggregates. Overall, these findings indicate that RICs provide a necessary microenvironment for rapid nephrogenesis during nephron regeneration.

Data availability

The authors declare that all data supporting the findings of this study are available within the article and its supplementary information files. Sequencing data have been deposited in GEO under accession codes GSE183382 and GSE191068.

The following data sets were generated

Article and author information

Author details

  1. Xiaoliang Liu

    Department of Nephrology, Army Medical University, Chongqing, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4239-9879
  2. Ting Yu

    Department of Respiratory Medicine, Army Medical University, Chongqing, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Xiaoqin Tan

    Department of Nephrology, Army Medical University, Chongqing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Daqing Jin

    Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Wenmin Yang

    Department of Nephrology, Army Medical University, Chongqing, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Jiangping Zhang

    Department of Nephrology, Army Medical University, Chongqing, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Lu Dai

    Department of Nephrology, Army Medical University, Chongqing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Zhongwei He

    Department of Nephrology, Army Medical University, Chongqing, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Dongliang Li

    Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Yunfeng Zhang

    Department of Nephrology, Army Medical University, Chongqing, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Shuyi Liao

    Department of Nephrology, Army Medical University, Chongqing, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3137-4403
  12. Jinghong Zhao

    Department of Nephrology, Army Medical University, Chongqing, China
    For correspondence
    zhaojh@tmmu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9750-3285
  13. Tao P Zhong

    Shanghai Key Laboratory of Regulatory Biology, East China Normal University, Shanghai, China
    For correspondence
    tzhong@bio.ecnu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
  14. Chi Liu

    Department of Nephrology, Army Medical University, Chongqing, China
    For correspondence
    chiliu@tmmu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2057-9649

Funding

National Key Research and Development Program of China (2017YFA0106600)

  • Chi Liu

National Natural Science Foundation of China (32070822)

  • Chi Liu

National Natural Science Foundation of China (82030023)

  • Jinghong Zhao

National Natural Science Foundation of China (31771609)

  • Chi Liu

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

Reviewing Editor

  1. Oliver Wessely

Ethics

Animal experimentation: In this study, all animal care and use protocol was approved by the Institutional Animal Careand Use Committee of the Army Medical University, China (SYXK-PLA-2007035).

Version history

  1. Preprint posted: August 28, 2021 (view preprint)
  2. Received: June 27, 2022
  3. Accepted: January 13, 2023
  4. Accepted Manuscript published: January 16, 2023 (version 1)
  5. Version of Record published: February 21, 2023 (version 2)

Copyright

© 2023, Liu 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. Xiaoliang Liu
  2. Ting Yu
  3. Xiaoqin Tan
  4. Daqing Jin
  5. Wenmin Yang
  6. Jiangping Zhang
  7. Lu Dai
  8. Zhongwei He
  9. Dongliang Li
  10. Yunfeng Zhang
  11. Shuyi Liao
  12. Jinghong Zhao
  13. Tao P Zhong
  14. Chi Liu
(2023)
Renal interstitial cells promote nephron regeneration by secreting prostaglandin E2
eLife 12:e81438.
https://doi.org/10.7554/eLife.81438

Share this article

https://doi.org/10.7554/eLife.81438

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