Zebrafish Development and Disease Models Laboratory, GIGA-Stem Cells, University of Liège, Liège, Belgium
David Bergemann
Zebrafish Development and Disease Models Laboratory, GIGA-Stem Cells, University of Liège, Liège, Belgium
Arnaud Lavergne
Zebrafish Development and Disease Models Laboratory, GIGA-Stem Cells, University of Liège, Liège, Belgium; GIGA-Genomics Core Facility, GIGA, University of Lièg, Liège, Belgium
Célia Reynders
Zebrafish Development and Disease Models Laboratory, GIGA-Stem Cells, University of Liège, Liège, Belgium
Caroline Désiront
Zebrafish Development and Disease Models Laboratory, GIGA-Stem Cells, University of Liège, Liège, Belgium
Chiara Goossens
Zebrafish Development and Disease Models Laboratory, GIGA-Stem Cells, University of Liège, Liège, Belgium
Lydie Flasse
Zebrafish Development and Disease Models Laboratory, GIGA-Stem Cells, University of Liège, Liège, Belgium
Bernard Peers
Zebrafish Development and Disease Models Laboratory, GIGA-Stem Cells, University of Liège, Liège, Belgium
Marianne M Voz
Zebrafish Development and Disease Models Laboratory, GIGA-Stem Cells, University of Liège, Liège, Belgium
Stimulation of pancreatic beta cell regeneration could be a therapeutic lead to treat diabetes. Unlike humans, the zebrafish can efficiently regenerate beta cells, notably from ductal pancreatic progenitors. To gain insight into the molecular pathways involved in this process, we established the transcriptomic profile of the ductal cells after beta cell ablation in the adult zebrafish. These data highlighted the protein phosphatase calcineurin (CaN) as a new potential modulator of beta cell regeneration. We showed that CaN overexpression abolished the regenerative response, leading to glycemia dysregulation. On the opposite, CaN inhibition increased ductal cell proliferation and subsequent beta cell regeneration. Interestingly, the enhanced proliferation of the progenitors was paradoxically coupled with their exhaustion. This suggests that the proliferating progenitors are next entering in differentiation. CaN appears as a guardian which prevents an excessive progenitor proliferation to preserve the pool of progenitors. Altogether, our findings reveal CaN as a key player in the balance between proliferation and differentiation to enable a proper beta cell regeneration.