PUBLICATION
Negative cell cycle regulation by calcineurin is necessary for proper beta cell regeneration in zebrafish
- Authors
- Massoz, L., Bergemann, D., Lavergne, A., Reynders, C., Désiront, C., Goossens, C., Flasse, L., Peers, B., Voz, M.M., Manfroid, I.
- ID
- ZDB-PUB-241011-5
- Date
- 2024
- Source
- eLIFE 12: (Journal)
- Registered Authors
- Bergemann, David, Lavergne, Arnaud, Manfroid, Isabelle, Peers, Bernard, Voz, Marianne
- Keywords
- beta cell, developmental biology, progenitor, regeneration, regenerative medicine, stem cells, zebrafish
- Datasets
- GEO:GSE212124
- MeSH Terms
-
- Cell Cycle
- Cell Proliferation*
- Regeneration*
- Gene Expression Profiling
- Insulin-Secreting Cells*/metabolism
- Insulin-Secreting Cells*/physiology
- Animals
- Zebrafish*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Cell Differentiation
- Calcineurin*/genetics
- Calcineurin*/metabolism
- PubMed
- 39383064 Full text @ Elife
Citation
Massoz, L., Bergemann, D., Lavergne, A., Reynders, C., Désiront, C., Goossens, C., Flasse, L., Peers, B., Voz, M.M., Manfroid, I. (2024) Negative cell cycle regulation by calcineurin is necessary for proper beta cell regeneration in zebrafish. eLIFE. 12:.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping