{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE316nnn/GSE316346/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Mus musculus"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE316346"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"TGFβ1 and Oncostatin M promotes the organization of two distinct stromal niches controlling different EMT states [Xenium]","description":"Epithelial-to-mesenchymal transition (EMT), a cellular process where epithelial cells acquire mesenchymal features, plays a key role in promoting tumor progression, metastasis and resistance to therapy. EMT is not a binary process and encompass a continuum of tumor states passing through intermediate hybrid states displaying different tumor functions. Although several intrinsic factors that regulate EMT have been identified, the extrinsic regulation and the precise dialogue between the tumor microenvironment (TME) and the different EMT states remain poorly understood. To unravel how the different components of the TME regulate the different EMT states, we performed single-cell RNA-sequencing and spatial transcriptomic of skin tumors presenting different degree of EMT. We uncover that different EMT states are associated with different niches containing different immune cell types. Neutrophils are more abundant in niche associated with hybrid EMT whereas macrophages, endothelial and lymphatic cells are more abundant in niche associated with more advanced EMT states. Bioinformatic prediction of the ligand-receptor pairs that regulate the communication between immune and tumor cells identified oncostatin M (OSM) as secreted by neutrophils and macrophages and interacted with hybrid EMT state whereas TGFβ1 expressed by macrophages and other stromal cells communicated with late EMT states. Functional validation showed that unlike TGFβ1, which only upregulated EMT program and promotes late EMT state, OSM partially activates EMT transcription factors while sustaining the epithelial program, promoting hybrid EMT states. In addition, both OSM and TGFβ1 function in a feed-forward manner by creating distinct inflammatory niches to maintain specific EMT states. Altogether, our results reveal that different niches are associated with different EMT states, and different signaling pathways sustain the creation of their own niche by attracting different immune cells.","dates":{"publication":"2026/09/17"},"accession":"GSE316346","cross_references":{"GSM":["GSM9450633","GSM9927082"],"GPL":["33896"],"GSE":["316346"],"taxon":["Mus musculus"]}}