Frizzled5 controls murine intestinal epithelial cell plasticity through organization of chromatin accessibility.

ABSTRACT: The homeostasis of the intestinal epithelium relies on intricate yet insufficiently understood mechanisms of intestinal epithelial plasticity. Here, we elucidate the pivotal role of Frizzled5 (Fzd5), a Wnt pathway receptor, as a determinant of murine intestinal epithelial cell fate. Deletion of Fzd5 in Lgr5⁺ intestinal stem cells (ISCs) impairs their self-renewal, whereas its deletion in Krt19⁺ cells disrupts lineage generation, without affecting crypt integrity in either case. However, a broader deletion of Fzd5 across the epithelium leads to substantial crypt deterioration. Integrated analysis of single-cell RNA sequencing (scRNA-seq) and single-cell ATAC-seq (scATAC-seq) identifies that Fzd5 governs chromatin accessibility, orchestrating the regulation of stem- and

SUBMITTER: Deng L 

PROVIDER: S-EPMC11794035 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature