Developmental beta-cell death orchestrates the islet's inflammatory milieu by regulating immune system crosstalk

ABSTRACT: While pancreatic beta-cell proliferation has been extensively studied, the role of cell death during islet development remains incompletely understood. Using a genetic model of caspase inhibition in beta cells coupled with mathematical modeling, we here discover an onset of beta cell death in juvenile zebrafish, which regulates beta cell mass. Histologically, this beta-cell death is underestimated due to phagocytosis by resident macrophages. To investigate beta-cell apoptosis at the molecular level, we implement a conditional model of beta-cell death linked to Ca2+ overload. Transcriptomic analysis reveals that metabolically-stressed beta-cells follow paths to either de-differentiation or apoptosis. Beta-cells destined to die activate inflammatory and immuno-regulatory pathways, suggesting

SUBMITTER: Dr. Nikolay Ninov 

PROVIDER: S-SCDT-10_1038-S44318-024-00332-W | biostudies-other |

REPOSITORIES: biostudies-other