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

Autor: Claudio Andrés Carril Pardo, Laura Massoz, Marie A Dupont, David Bergemann, Jordane Bourdouxhe, Arnaud Lavergne, Estefania Tarifeño-Saldivia, Christian SM Helker, Didier YR Stainier, Bernard Peers, Marianne M Voz, Isabelle Manfroid
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: eLife, Vol 11 (2022)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.67576
Popis: 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.
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