A δ-cell subpopulation with pro-β cell identity contributes to efficient age-independent recovery in a zebrafish diabetes model
- University of Liège, Belgium
- University of Concepción, Chile
- 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
Article and author information
Author details
Didier YR Stainier true
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).
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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