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A niche-dependent redox rheostat regulates epithelial stem cell fate in the distal colon II

GSE289397 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2025/02/17 Platform GPL24247
Summary
The niche environment surrounding intestinal stem cells (ISCs) varies along the length of intestine and provides key cues that regulate stem cell fate. Here, we investigated the role of cellular redox balance in colonic ISC function. We show that hypoxia and Wnt signaling synergize to restrict the reactive oxygen species (ROS) generating enzyme NADPH oxidase 1 (NOX1) to the crypt base in the distal colon. NOX1 function maintains a more oxidative cell state that licenses cell cycle entry, altering the balance of asymmetric stem cell self-renewal and directing lineage commitment. Mechanistically, cell redox state directs a self-reinforcing circuit that connects hypoxia inducible factor 1 (HIF1a)-dependent signaling with regulation of the metabolic enzyme isocitrate dehydrogenase 1 (IDH1). Our studies show that cellular redox balance is a central and niche-dependent regulator of epithelial homeostasis and regeneration and provide a basis for understanding disease propensity in the distal large intestine.
Published in
A niche-dependent redox rheostat regulates epithelial stem cell fate
Chen X, Raghunathan K, Bao B et al. · Nature communications 2025 · PMID 41315209 · doi:10.1038/s41467-025-66636-5
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Also filed as BioProject PRJNA1222854 and SRA study SRP563450. Searching any of these in the dataset finder brings you back here.

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