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

Autor: Arnaud Lavergne, Isabelle Manfroid, Bernard Peers, David Bergemann, Estefanía Tarifeño-Saldivia, Marianne Voz, Carril Pardo Ca, Didier Y.R. Stainier, Helker Csm, Jordane Bourdouxhe, Laura Massoz, Dupont M
Rok vydání: 2021
Předmět:
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 are Somatostatin+ Insulin+, but are nevertheless functional and normalize glycemia. These bihormonal cells are transcriptionally close to a subset of δ-cells in normal islets characterized by the expression of somatostatin 1.1 (sst1.1), the β-cell genes pdx1, slc2a2 and gck, and the machinery for glucose-induced Insulin secretion. β-cell destruction triggers massive sst1.1 δ-cell conversion to bihormonal cells. Our work shows that their pro- β-cell identity predisposes this zebrafish δ-cell subpopulation to efficient age-independent neogenesis of Insulin-producing cells and provides clues to restoring functional β-cells in mammalian diabetes models.
Databáze: OpenAIRE