Renal interstitial cells promote nephron regeneration by secreting prostaglandin E2
- Army Medical University, China
- East China Normal University, China
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.
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adult zebrafish kidney cellsNCBI Gene Expression Omnibus, GSE183382.
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Zebrafish kidney regeneration transcriptomeNCBI Gene Expression Omnibus, GSE191068.
Article and author information
Author details
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
- 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
- Preprint posted: August 28, 2021 (view preprint)
- Received: June 27, 2022
- Accepted: January 13, 2023
- Accepted Manuscript published: January 16, 2023 (version 1)
- 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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Renal interstitial cells promote nephron regeneration by secreting prostaglandin E2
eLife 12:e81438.
https://doi.org/10.7554/eLife.81438
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