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Single-cell transcriptome profiling of mouse colonic mucosa in colitis

ABSTRACT: Chronic injury and inflammation pose high risks for epithelial dysplasia and cancer. In the “field cancerization” model, spontaneous mutations confer a stem-cell fitness advantage and promote gradual clonal expansion. Here, through 3d imaging, fate-mapping, biophysical modeling, and single-cell transcriptomics in a mouse model of acute colitis, we define an alternate, rapid mechanism for clonal expansion: the neutral activation of metabolically reprogrammed “founder progenitor cells” (FPCs) during wound healing. FPCs leverage the breakdown of normal crypt regenerative boundaries to expand multiplicatively into new crypts patterned from a zone of cellular mixing and plasticity. FPCs represent relatively generic proliferative cells probabilistically emerging from a background of fetal-reprogrammed epithelium and derive from both surface and basal zones of the injured colonic mucosa. Acute wound healing activates spatial and lineage plasticity to generate clonal fields without significant mutational burden. These results suggest that hallmark pre-neoplastic changes may arise from a punctuated pattern of injury and healing rather than gradual field cancerization.

ORGANISM(S): Mus musculus

PROVIDER: GSE193342 | GEO | 2023/07/14

REPOSITORIES: GEO

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