A δ-cell subpopulation with pro-β cell identity contributes to efficient age-independent recovery in a zebrafish diabetes model

  1. Claudio Andrés Carril Pardo
  2. Laura Massoz
  3. Marie A Dupont
  4. David Bergemann
  5. Jordane Bourdouxhe
  6. Arnaud Lavergne
  7. Estefania Tarifeño-Saldivia
  8. Christian SM Helker
  9. Didier YR Stainier true
  10. Bernard Peers
  11. Marianne M Voz
  12. Isabelle Manfroid  Is a corresponding author
  1. University of Liège, Belgium
  2. University of Concepción, Chile
  3. Max Planck Institute for Heart and Lung Research, Germany

Abstract

Restoring damaged b-cells in diabetic patients by harnessing the plasticity of other pancreatic cells raises the questions of the efficiency of the process and of the functionality of the new Insulin-expressing cells. To overcome the weak regenerative capacity of mammals, we used regeneration-prone zebrafish to study b-cells arising following destruction. We show that most new insulin cells differ from the original b-cells as they coexpress Somatostatin and Insulin. These bihormonal cells are abundant, functional and able to normalize glycemia. Their formation in response to b-cell destruction is fast, efficient and age-independent. Bihormonal cells are transcriptionally close to a subset of d-cells that we identified in control islets and which are characterized by the expression of somatostatin 1.1 (sst1.1) and by genes essential for glucose-induced Insulin secretion in β-cells such as pdx1, slc2a2 and gck. We observed in vivo the conversion of monohormonal sst1.1-expressing cells to sst1.1+ ins+ bihormonal cells following b-cell destruction. Our findings support the conclusion that sst1.1 d-cells possess a pro-b identity enabling them to contribute to the neogenesis of Insulin-producing cells during regeneration. This work unveils that abundant and functional bihormonal cells benefit to diabetes recovery in zebrafish.

Data availability

RNA sequencing data have been deposited at NCBI GEO

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Claudio Andrés Carril Pardo

    Zebrafish Development and Disease Models laboratory, GIGA-Stem Cells, University of Liège, Liège, Belgium
    Competing interests
    No competing interests declared.
  2. Laura Massoz

    Zebrafish Development and Disease Models laboratory, GIGA-Stem Cells, University of Liège, Liège, Belgium
    Competing interests
    No competing interests declared.
  3. Marie A Dupont

    Zebrafish Development and Disease Models laboratory, GIGA-Stem Cells, University of Liège, Liège, Belgium
    Competing interests
    No competing interests declared.
  4. David Bergemann

    Zebrafish Development and Disease Models laboratory, GIGA-Stem Cells, University of Liège, Liège, Belgium
    Competing interests
    No competing interests declared.
  5. Jordane Bourdouxhe

    Zebrafish Development and Disease Models laboratory, GIGA-Stem Cells, University of Liège, Liège, Belgium
    Competing interests
    No competing interests declared.
  6. Arnaud Lavergne

    GIGA-Genomics core facility, University of Liège, Liège, Belgium
    Competing interests
    No competing interests declared.
  7. Estefania Tarifeño-Saldivia

    Department of Biochemistry and Molecular Biology, University of Concepción, Concepción, Chile
    Competing interests
    No competing interests declared.
  8. Christian SM Helker

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    No competing interests declared.
  9. Didier YR Stainier true

    Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
    Competing interests
    Didier YR Stainier, Senior editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0382-0026
  10. Bernard Peers

    Zebrafish Development and Disease Models laboratory, GIGA-Stem Cells, University of Liège, Liège, Belgium
    Competing interests
    No competing interests declared.
  11. Marianne M Voz

    Zebrafish Development and Disease Models laboratory, GIGA-Stem Cellslls, University of Liège, Liège, Belgium
    Competing interests
    No competing interests declared.
  12. Isabelle Manfroid

    Zebrafish Development and Disease Models laboratory, GIGA-Stem Cells, University of Liège, Liège, Belgium
    For correspondence
    Isabelle.Manfroid@uliege.be
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3445-3764

Funding

Chilean National Agency for Research and Development , Becas Chile (Scholarship,72170660)

  • Claudio Andrés Carril Pardo

National Belgian Funds for Scientific Research (FRIA PhD fellowship)

  • Arnaud Lavergne

National Belgian Funds for Scientific Research (FRIA PhD fellowship)

  • Laura Massoz

National Belgian Funds for Scientific Research (EoS Program,30826052)

  • Marie A Dupont

National Belgian Funds for Scientific Research (FRIA PhD fellowship)

  • David Bergemann

National Belgian Funds for Scientific Research (EoS Program,30826052)

  • Jordane Bourdouxhe

European Regional Development Fund (Biomed Hub Technology Support,2.2.1/996)

  • Arnaud Lavergne

National Belgian Funds for Scientific Research

  • Bernard Peers

National Belgian Funds for Scientific Research

  • Isabelle Manfroid

National Belgian Funds for Scientific Research

  • Marianne M Voz

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

Ethics

Animal experimentation: All experiments were carried out in compliance with the European Union and Belgian law and with the approval of the ULiège Ethical Committee for experiments with laboratory animals (approval numbers 14-1662, 16-1872, 19-2083, 21-2353).

Reviewing Editor

  1. Lori Sussel, University of Colorado Anschutz Medical Campus, United States

Publication history

  1. Received: February 15, 2021
  2. Preprint posted: June 24, 2021 (view preprint)
  3. Accepted: January 20, 2022
  4. Accepted Manuscript published: January 21, 2022 (version 1)
  5. Version of Record published: February 7, 2022 (version 2)

Copyright

© 2022, Carril Pardo 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. Claudio Andrés Carril Pardo
  2. Laura Massoz
  3. Marie A Dupont
  4. David Bergemann
  5. Jordane Bourdouxhe
  6. Arnaud Lavergne
  7. Estefania Tarifeño-Saldivia
  8. Christian SM Helker
  9. Didier YR Stainier true
  10. Bernard Peers
  11. Marianne M Voz
  12. Isabelle Manfroid
(2022)
A δ-cell subpopulation with pro-β cell identity contributes to efficient age-independent recovery in a zebrafish diabetes model
eLife 11:e67576.
https://doi.org/10.7554/eLife.67576

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