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Iron deficiency induces maturation-dependent loss of pancreatic β-cells.

GSE296435 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2025/12/23 Platform GPL24247
Summary
Pancreatic β-cells maintain glucose homeostasis by secreting insulin in response to rising blood glucose, a process fueled by mitochondrial ATP production. Iron, a core cofactor in the electron transport chain, is essential for this metabolic coupling. While the cytotoxic effects of iron overload are well known, the role of iron sufficiency during β-cell development remains unclear. Here, we identify a maturation-dependent requirement for iron in mouse and human β-cells. Using chemical chelation and genetic disruption of transferrin receptor (TFRC)-mediated uptake, we show that immature β-cells depend on iron during metabolic transition to functional maturity. Iron restriction at this stage impairs oxidative metabolism and compromises survival. In contrast, mature β-cells remain resilient to iron depletion, revealing a developmental switch in iron dependency. These findings establish iron as a key metabolic cue in β-cell development and suggest strategies to generate fully functional stem cell-derived β-cells for diabetes modeling and cell replacement therapy.
Published in
Iron deficiency induces maturation-dependent loss of pancreatic β-cells
Van Mulders A, Willems L, Coenen S et al. · Nature communications 2026 · PMID 41698932 · doi:10.1038/s41467-026-69574-y
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Also filed as BioProject PRJNA1259380 and SRA study SRP583342. Searching any of these in the dataset finder brings you back here.

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