Tracing oncogene-driven remodeling of the intestinal stem cell niche

Interactions between tumor cells and the surrounding microenvironment contribute to tumor progression, metastasis and recurrence. Here, we present an oncogene-associated, multicolor reporter mouse model, the Red2Onco system, that allows differential tracing of mutant and wild-type cells in the same tissue. We show that oncogene-expressing mutant crypts alter the cellular organization of neighbouring wild-type crypts, driving accelerated clonal drift in the intestinal epithelium. Through the comparative single-cell transcriptomic analysis of Red2Onco system, we show how environmental changes in the shared niche, mediated by direct and indirect signals from oncogene-expressing clones, promote the accelerated differentiation of wild-type stem cells.

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Tracing oncogene-driven remodeling of the intestinal stem cell niche

Interactions between tumor cells and the surrounding microenvironment contribute to tumor progression, metastasis and recurrence.

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