A δ-cell subpopulation with pro-β cell identity contributes to efficient age-independent recovery in a zebrafish diabetes model
- Carril Pardo, C.A., Massoz, L., Dupont, M.A., Bergemann, D., Bourdouxhe, J., Lavergne, A., Tarifeño-Saldivia, E., Helker, C.S., Stainier, D.Y., Peers, B., Voz, M.M., Manfroid, I.
- eLIFE 11: (Journal)
- Registered Authors
- Bergemann, David, Bourdouxhe, Jordane, Dupont, Marie, Helker, Christian, Lavergne, Arnaud, Manfroid, Isabelle, Peers, Bernard, Stainier, Didier, Voz, Marianne
- cell biology, zebrafish
- MeSH Terms
- Diabetes Mellitus, Experimental/metabolism*
- Insulin-Secreting Cells/metabolism*
- Somatostatin-Secreting Cells/metabolism*
- 35060900 Full text @ Elife
Carril Pardo, C.A., Massoz, L., Dupont, M.A., Bergemann, D., Bourdouxhe, J., Lavergne, A., Tarifeño-Saldivia, E., Helker, C.S., Stainier, D.Y., Peers, B., Voz, M.M., Manfroid, I. (2022) A δ-cell subpopulation with pro-β cell identity contributes to efficient age-independent recovery in a zebrafish diabetes model. eLIFE. 11:.
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.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes