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Dedifferentiation-Driven Oncogenic Stemness Promotes Tumor-Sustaining Adaptability in the Intestinal Epithelium

GSE263192 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/10/27 Platform GPL24247
Summary
Intestinal tumors can arise either from mutations sustained in Lgr5⁺ stem cells (bottom-up) or through dedifferentiation of lineage-committed epithelial cells (top-down). Using a Smad4 loss-of-function and β-catenin gain-of-function mutant mouse model, we show that dedifferentiation-derived stem cells sustain tumorigenesis more effectively than mutant Lgr5⁺ cells in the endogenous crypts. Bulk and single-cell RNA sequencing revealed transcriptional reprogramming and the emergence of oncogenic villus-derived stem-like cells. Complementary in vivo and organoid studies suggest that dedifferentiation-derived oncogenic stem cells possess superior tumor-initiating and sustaining capacity.
Published in
Dedifferentiation-driven oncogenic stemness promotes tumor-sustaining adaptability in the intestinal epithelium
Zgeib K, Hui T, Garcia S et al. · Cell death & disease 2026 · PMID 41997917 · doi:10.1038/s41419-026-08669-2
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Also filed as BioProject PRJNA1096110 and SRA study SRP499657. Searching any of these in the dataset finder brings you back here.

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