Article (Scientific journals)
Negative cell cycle regulation by Calcineurin is necessary for proper beta cell regeneration in zebrafish
Massoz, Laura; Bergemann, David; Lavergne, Arnaud et al.
2023In eLife
Peer reviewed
 

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Abstract :
[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Massoz, Laura  ;  Université de Liège - ULiège > GIGA > GIGA Stem Cells - Zebrafish Development and Disease Model
Bergemann, David ;  Université de Liège - ULiège > Unités de recherche interfacultaires > GIGA-Research
Lavergne, Arnaud  ;  Université de Liège - ULiège > Département de gestion vétérinaire des Ressources Animales (DRA) > Génomique animale
Reynders, Célia  ;  Université de Liège - ULiège > GIGA
Désiront, Caroline ;  Université de Liège - ULiège > GIGA > GIGA Stem Cells - Zebrafish Development and Disease Model
Goossens, Chiara ;  Université de Liège - ULiège > Département des sciences de la vie
Flasse, Lydie ;  Université de Liège - ULiège > GIGA > GIGA Stem Cells - Zebrafish Development and Disease Model
Peers, Bernard ;  Université de Liège - ULiège > Département des sciences de la vie
Voz, Marianne  ;  Université de Liège - ULiège > GIGA > GIGA Stem Cells - Zebrafish Development and Disease Model
Manfroid, Isabelle ;  Université de Liège - ULiège > GIGA > GIGA Stem Cells - Zebrafish Development and Disease Model
Language :
English
Title :
Negative cell cycle regulation by Calcineurin is necessary for proper beta cell regeneration in zebrafish
Publication date :
14 August 2023
Journal title :
eLife
Publisher :
eLife Sciences Publications, Ltd
Peer reviewed :
Peer reviewed
Available on ORBi :
since 31 January 2024

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