{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE300nnn/GSE300523/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE300523"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Stromal Hedgehog signaling drives segment-specific malignant transformation of gastrointestinal stem cells by producing BMP antagonists","description":"Hedgehog (HH) signaling plays a complex role in epithelial-stromal interactions, but its effects on gastrointestinal stem cells mediated by the heterogeneous stromal cell populations remain incompletely understood. Here, we found that genetic activation of HH signaling in stromal cells marked by Col1a2, Pdgfra, or Gli1, but not by Acta2, induces tumorigenesis in the stomach and gastroesophageal junction, but not in small or large intestines. HH signaling increases the expression of multiple BMP antagonists in gastric but not colonic stromal cells via Gli1-mediated transcription. These BMP antagonists in turn activate Wnt-β-catenin signaling in gastric stem cells, driving their proliferation and initiating gastric cancer expressing CD44 and Sox9 but not Lgr5. Activating BMP or inhibiting Wnt signaling blocks tumor initiation. TCGA patient data analysis reveals elevated HH signaling in gastric cancers, which correlates with suppressed BMP signaling. These findings uncover an gastrointestinal segment-specific oncogenic role for HH signaling in Pdgfra+Acta2- stromal cells, mediated through the BMP-Wnt/-catenin axis.","dates":{"publication":"2026/09/30"},"accession":"GSE300523","cross_references":{"GSM":["GSM9063835","GSM9063834","GSM9063831","GSM9063830","GSM9063833","GSM9063832"],"GPL":["23479"],"GSE":["300523"],"taxon":["Mus musculus"],"PMID":["[42556639]"]}}