GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE287nnn/GSE287338/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE287338GEOGSEfalseDynamic Reprogramming of Stromal Pdgfra-expressing cells during WNT-Mediated Transformation of the Intestinal Epithelium [Figure 2]Stromal fibroblasts of the mesenchyme regulate critical signaling gradients along the crypt-villus axis1 and provide a niche that supports intestinal stem cells in the intestine. Here we report that Pdgfra-expressing fibroblasts secrete ligands that promote a fetal-like state in the intestinal mucosa during early WNT-mediated tumorigenesis. Using a mouse model of WNT-driven oncogenesis and single-cell RNA sequencing (RNA-seq) of mesenchyme cell populations, we revealed a dynamic reprogramming of Pdgfra+ fibroblasts that facilitates WNT-mediated tissue transformation. Functional assays of potential mediators of cell-to-cell communication between these fibroblasts and the oncogenic epithelium revealed that TGFB signaling is notably induced in Pdgfra+ fibroblasts in the presence of oncogenic epithelium, and TGFB was essential to sustain fetal-like growth of organoids ex vivo. Genetic reduction of Cdx2 in the β-catenin mutant epithelium elevated the fetal-like transcriptome and accelerated WNT-dependent onset of oncogenic transformation of the tissue in vivo. These results demonstrate that Pdgfra+ fibroblasts are activated during WNT-driven oncogenesis to promote a fetal-like state in the epithelium that precedes and facilitates formation of tumors.2026/04/28GSE287338GSM8744531GSM8744530GSM8744529GSM8744528GSM874452734328287338Mus musculus[41784677]