{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE308nnn/GSE308537/"]},"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=GSE308537"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Rspo mutations skew intestinal secretory cell fate, enhance cell stemness and are preferentially selected in colitis-associated dysplasia","description":"Aberrant Wnt activation is a hallmark of colorectal neoplasia, however the mechanism by which this disruption occurs is variable and influenced by the cell-of-origin context and selected mutation type. Mutation type varies from lesion to lesion, with different mutations preferentially acquired in different intestinal neoplasia subtypes. Here, we assessed the Wnt pathway mutation landscape across different sporadic and colitis-associated lesions to understand the variable capacity of different Wnt disrupting mutations to initiate neoplasia. We then used mouse models to compare the impact of Apc (ligand-independent) and Rspo-overexpression (ligand-dependent) mutations on secretory and stem cell fate dynamics. In contrast with the effect of Apc mutation, which generates super-competing, niche seceding stem cells in sporadic disease, epithelial Rspo3 expression favours Paneth cell differentiation and supports the generation of new Wnt ligand-dependent intestinal stem cell niches. These support ectopic stem cell functionality, which provides a context-specific fitness advantage in a colonic regeneration setting.","dates":{"publication":"2026/09/01"},"accession":"GSE308537","cross_references":{"GSM":["GSM9247724","GSM9247725","GSM9247726","GSM9247727","GSM9247720","GSM9247721","GSM9247722","GSM9247723","GSM9247717","GSM9247718","GSM9247719","GSM9247697","GSM9247730","GSM9247735","GSM9247736","GSM9247737","GSM9247738","GSM9247731","GSM9247698","GSM9247732","GSM9247699","GSM9247733","GSM9247734","GSM9247728","GSM9247729","GSM9247740","GSM9247741","GSM9247746","GSM9247702","GSM9247703","GSM9247747","GSM9247704","GSM9247748","GSM9247749","GSM9247705","GSM9247742","GSM9247743","GSM9247700","GSM9247744","GSM9247701","GSM9247745","GSM9247739","GSM9247750","GSM9247751","GSM9247752","GSM9247713","GSM9247714","GSM9247715","GSM9247716","GSM9247753","GSM9247754","GSM9247710","GSM9247711","GSM9247755","GSM9247712","GSM9247706","GSM9247707","GSM9247708","GSM9247709"],"GPL":["19057"],"GSE":["308537"],"taxon":["Mus musculus"]}}