Dynamic Intestinal Stem Cell Plasticity and Lineage Remodeling by a Nutritional Environment Relevant to Human Risk for Tumorigenesis.

ABSTRACT: New Western-style diet 1 (NWD1), a purified diet establishing mouse exposure to key nutrients recapitulating levels that increase human risk for intestinal cancer, reproducibly causes mouse sporadic intestinal and colonic tumors reflecting human etiology, incidence, frequency, and lag with developmental age. Complex NWD1 stem cell and lineage reprogramming was deconvolved by bulk and single-cell RNA sequencing, single-cell Assay for Transposase-Accessible Chromatin using sequencing, functional genomics, and imaging. NWD1 extensively, rapidly, and reversibly, reprogrammed Lgr5hi stem cells, epigenetically downregulating Ppargc1a expression, altering mitochondrial structure and function. This suppressed Lgr5hi stem cell functions and developmental maturation of Lgr5hi cell progeny as cells p

SUBMITTER: Choi J 

PROVIDER: S-EPMC10390890 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature