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Transient ER stress cell-autonomously promotes beta cell cycling

GSE274443 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/12/19 Platform GPL24247
Summary
Regenerating endogenous pancreatic ß-cells is a potentially curative yet currently elusive strategy for diabetes therapy. Mimicking the microenvironment of the developing pancreas and leveraging vascular signals that support pancreatic endocrinogenesis may promote ß-cell regeneration. We aimed to investigate whether recovery from experimental hypovascularization of the endocrine pancreas, achieved by modulating the transgenic production of a VEGF-A blocker in ß-cells, could trigger mouse ß-cell proliferation. Serendipitously, we found that transgene overexpression in ß-cells induces endoplasmic reticulum (ER) stress and that subsequent relief from this stress stimulates ß-cell proliferation independent of vessel recovery. Transient GFP overexpression in vivo and transient chemical induction of ER stress in vitro replicated this ß-cell cycling response. Our findings highlight the potential side effects of ER stress due to transgene overexpression in ß-cells and assert that ER stress relief serves as a potent regenerative stimulus.
Published in
Transient ER stress cell-autonomously promotes beta cell cycling in mice
Bourgeois S, Van Mulders A, Heremans Y et al. · Diabetologia 2026 · PMID 41537777 · doi:10.1007/s00125-025-06649-3
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Also filed as BioProject PRJNA1146436 and SRA study SRP525412. Searching any of these in the dataset finder brings you back here.

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