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Single cell sequencing of mouse gastric cell populations

ABSTRACT: Although gastric cancer is a leading cause of cancer-related deaths, systemic treatment strategies remain scarce. Here, we report the pro-tumorigenic properties of the crosstalk between intestinal tuft cells and type 2 innate lymphoid cells (ILC2) that is evolutionarily optimized for epithelial remodeling in response to helminth infection. We demonstrate that tuft cell-derived interleukin 25 (IL25) drives ILC2 activation, inducing the release of IL13 and promoting tuft cell hyperplasia. This reciprocal tuft cell - ILC2 circuit promotes early gastric metaplasia and tumor formation while genetic ablation of tuft cells, ILC2s or therapeutic targeting of IL13 or IL25 alleviates these phenotypes. Importantly, tuft cell and ILC2 gene signatures predict worsening survival in intestinal-type gastric cancer patients, with ~50% of these tumors showing enrichment for tuft cells and ILC2s. Thus, we reveal an unanticipated function of the tuft cell - ILC2 circuit in promoting multiple steps towards gastric carcinogenesis. Together, this may provide an opportunity to therapeutically inhibit early-stage gastric cancer through repurposing antibody-mediated therapies.

ORGANISM(S): Mus musculus

PROVIDER: GSE217498 | GEO | 2023/09/25

REPOSITORIES: GEO

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