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

Author:

Carril Pardo Claudio Andrés1,Massoz Laura1,Dupont Marie A1,Bergemann David1,Bourdouxhe Jordane1,Lavergne Arnaud12,Tarifeño-Saldivia Estefania13,Helker Christian SM4,Stainier Didier YR4ORCID,Peers Bernard1,Voz Marianne M1,Manfroid Isabelle1ORCID

Affiliation:

1. Zebrafish Development and Disease Models laboratory, GIGA-Stem Cells, University of Liège

2. GIGA-Genomics core facility, University of Liège

3. Gene Expression and Regulation Laboratory, Department of Biochemistry and Molecular Biology, University of Concepción

4. Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research

Abstract

Restoring damaged β-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 β-cells arising following destruction. We show that most new insulin cells differ from the original β-cells as they coexpress Somatostatin and Insulin. These bihormonal cells are abundant, functional and able to normalize glycemia. Their formation in response to β-cell destruction is fast, efficient, and age-independent. Bihormonal cells are transcriptionally close to a subset of δ-cells that we identified in control islets and that 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 β-cell destruction. Our findings support the conclusion that sst1.1 δ-cells possess a pro-β 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.

Funder

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

Belgian National Fund for Scientific Research

National Belgian Funds for Scientific Research

European Regional Development Fund

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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