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

Carril Pardo, C. A.; Massoz, L.; Dupont, M.; Bergemann, D.; Bourdouxhe, J.; Lavergne, A.; Tarifeno-Saldivia, E.; Helker, C. S. M.; Stainier, D. Y. R.; Peers, B.; Voz, M. L.; Manfroid, I.

doi:10.1101/2021.06.24.449706

bioRxiv · 10.1101/2021.06.24.449706

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

Carril Pardo, C. A.·Massoz, L.·Dupont, M.·Bergemann, D.·Bourdouxhe, J.·Lavergne, A.·Tarifeno-Saldivia, E.·Helker, C. S. M.·Stainier, D. Y. R.·Peers, B.·Voz, M. L.·Manfroid, I.

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Abstract

Restoring damaged {beta}-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 {beta}-cells arising following destruction. We show that most new insulin cells differ from the original {beta}-cells as they are Somatostatin+ Insulin+, but are nevertheless functional and normalize glycemia. These bihormonal cells are transcriptionally close to a subset of {delta}-cells in normal islets characterized by the expression of somatostatin 1.1 (sst1.1), the {beta}-cell genes pdx1, slc2a2 and gck, and the machinery for glucose-induced Insulin secretion. {beta}-cell destruction triggers massive sst1.1 {delta}-cell conversion to bihormonal cells. Our work shows that their pro- {beta}-cell identity predisposes this zebrafish {delta}-cell subpopulation to efficient age-independent neogenesis of Insulin-producing cells and provides clues to restoring functional {beta}-cells in mammalian diabetes models.

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Carril Pardo, C. A., Massoz, L., Dupont, M., Bergemann, D., Bourdouxhe, J., Lavergne, A., Tarifeno-Saldivia, E., Helker, C. S. M., Stainier, D. Y. R., Peers, B., Voz, M. L., Manfroid, I.. 2021-06-24. A δ-cell subpopulation with a pro-β-cell identity confers efficient age-independent recovery in a zebrafish model of diabetes. https://doi.org/10.1101/2021.06.24.449706

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