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0This research utilizes single-cell analysis and organoid modeling to map how oncogenic mutations and microenvironmental signals co-regulate the fate of colonic stem cells. The study identifies a continuous phenoscape of epithelial differentiation, ranging from slow-cycling revival colonic stem cells (revCSCs) induced by stromal fibroblasts to hyper-proliferative cancer stem cells (proCSCs) driven by mutations. Findings reveal that while fibroblasts use TGF-β and YAP signaling to promote tissue plasticity, oncogenes like APC and KRAS eventually dominate this process. These mutations essentially decouple the epithelia from external regulation, trapping the cells in a pro-cancerous state by disrupting healthy cell-to-cell communication. Ultimately, the sources demonstrate that tumor development is characterized by the systematic obstruction of homeostatic stromal signals, which prevents epithelial cells from accessing regenerative states.
References:
Qin X, Rodriguez F C, Sufi J, et al. An oncogenic phenoscape of colonic stem cell polarization[J]. Cell, 2023, 186(25): 5554-5568. e18.
