{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE335nnn/GSE335053/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE335053"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Fibroblast-derived Spondin-2 promotes dysplastic transition in metaplastic gastric epithelial cells","description":"Background and Aims: Fibroblasts are increasingly recognized as active drivers of early gastric carcinogenesis, yet the specific fibroblast-derived factors that promote the transition from metaplasia to dysplasia remain unknown. We have recently found that coculture of metaplasia or cancer-derived fibroblasts with gastroids dominated by spasmolytic polypeptide-expressing metaplasia (SPEM) lineages leads to a decrease of metaplastic markers and a concomitant upregulation of dysplasia markers. We have now identified the matricellular protein Spondin-2 (SPON2) as a key fibroblast-secreted mediator of this transition. Methods: Single-cells RNAsequencing of patient-derived fibroblast populations and proteomic profiling of conditioned media were used to identify fibroblast-secreted factors. Spatial transcriptomics was used to evaluate localization of SPON2+ fibroblasts in human gastric tissue. Knockdown of SPON2 in cancer-derived fibroblasts was performed in coculture with SPEM lineage gastroids, and recombinant SPON2 treatment was applied to metaplastic gastroids. Results: Single-cell RNAsequencing and proteomic profiling revealed SPON2 as the most upregulated and selectively secreted protein in metaplasia- and cancer-derived fibroblasts compared to normal fibroblasts. Spatial transcriptomics demonstrated PDGFRA/SPON2 co-expressing fibroblasts localized adjacent to metaplastic glands in human gastric tissue. Knockdown of SPON2 in cancer-derived fibroblasts abrogated induction of dysplastic promotion in cocultured SPEM lineage gastroids, while preserving metaplastic markers. Conversely, recombinant SPON2 treatment promoted down-regulation of metaplastic markers and upregulation of dysplasia-associated proteins in metaplastic gastroids. Conclusions: These findings identify fibroblast-derived SPON2 as a potent secreted factor driving the metaplasia-to-dysplasia transition in gastric epithelium. Therefore, SPON2 represents the first fibroblast-derived secreted factor that can promote preneoplastic progression.","dates":{"publication":"2026/07/20"},"accession":"GSE335053","cross_references":{"GSM":["GSM9805063","GSM9805064","GSM9805065","GSM9805066","GSM9805067","GSM9805068"],"GPL":["34284"],"GSE":["335053"],"taxon":["Homo sapiens"]}}