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Akhtar2025 - Pancreatic beta-cell turnover


ABSTRACT: Beta-cells in the developing pancreas of zebrafish divide rapidly between 5 and 30 days post fertilization (dpf) and additional beta-cells are recruited to the islet of Langerhans. Yet their overall number by 30 dpf remains well under control and this control is achieved with the help of cell death, as was shown in the publication associated with this model. The spatio-temporal agent-based model is implemented in Morpheus (https://morpheus.gitlab.io). Moreover, this model combines four models of beta-cell turnover. One pair of models are ordinary differential equations for (the continuum approximation of) the beta-cell number, the other pair are two-dimensional agent-based models (in z-layers ‘0’ for wildtype and ‘2’ for the mutant, separated by a fixed layer ‘1’) that explore stochastic effects of the combined cell behaviors and visualize the spatial density of cell death events. Of each pair, one model corresponds to the wildtype with all processes active and the other to the p35 mutant where apoptosis is suppressed through caspase inhibition. Time unit is 1day (dpf) and spatial unit is 1µm. In the simulation results figures, wildtype zebrafish is shown left and the p35 mutant to the right. Time in dpf is given at the bottom right. Red color denotes quiescent and green denotes cycling beta-cells. Blue colored cells undergo apoptosis. For more results and details of the model, please see https://identifiers.org/morpheus/M2986

SUBMITTER: Lutz Brusch  

PROVIDER: MODEL2503030004 | BioModels | 2025-03-03

REPOSITORIES: BioModels

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Publications

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

Akhtar Mohammad Nadeem MN   Hnatiuk Alisa A   Delgadillo-Silva Luis L   Geravandi Shirin S   Sameith Katrin K   Reinhardt Susanne S   Bernhardt Katja K   Singh Sumeet Pal SP   Maedler Kathrin K   Brusch Lutz L   Ninov Nikolay N  

The EMBO journal 20250106 4


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 le  ...[more]

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