
Calcineurin modulates the balance between progenitor proliferation and differentiation to facilitate beta cell regeneration.


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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 as a new potential modulator of beta cell regeneration. We showed that calcineurin overexpression abolished the regenerative response, leading to glycemia dysregulation. On the opposite, calcineurin 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. Calcineurin appears as a guardian which prevents an excessive progenitor proliferation to preserve the pool of progenitors. Altogether, our findings reveal calcineurin as a key player in the balance between proliferation and differentiation to enable a proper beta cell regeneration.

### Competing Interest Statement

The authors have declared no competing interest.

Negative cell cycle regulation by Calcineurin is necessary for proper beta cell regeneration in zebrafish

calcineurin-s-role-in-zebrafish-beta-cell-regeneration


Calcineurin's Role in Zebrafish Beta Cell Regeneration
