{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yum MK"],"funding":["Cancer Research UK","European Research Council","Medical Research Council","Wellcome Trust"],"pagination":["442-447"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7614896"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["594(7863)"],"pubmed_abstract":["Interactions between tumour cells and the surrounding microenvironment contribute to tumour progression, metastasis and recurrence<sup>1-3</sup>. Although mosaic analyses in Drosophila have advanced our understanding of such interactions<sup>4,5</sup>, it has been difficult to engineer parallel approaches in vertebrates. Here we present an oncogene-associated, multicolour reporter mouse model-the Red2Onco system-that allows differential tracing of mutant and wild-type cells in the same tissue. By applying this system to the small intestine, we show that oncogene-expressing mutant crypts alter the cellular organization of neighbouring wild-type crypts, thereby driving accelerated clonal drift. Crypts that express oncogenic KRAS or PI3K secrete BMP ligands that suppress local stem cell activity, while changes in PDGFR<sup>lo</sup>CD81<sup>+</sup> stromal cells induced by crypts with oncogenic PI3K alter the WNT signalling environment. Together, these results show how oncogene-driven paracrine remodelling creates a niche environment that is detrimental to the maintenance of wild-type tissue, promoting field transformation dominated by oncogenic clones."],"journal":["Nature"],"pubmed_title":["Tracing oncogene-driven remodelling of the intestinal stem cell niche."],"pmcid":["PMC7614896"],"funding_grant_id":["639050","107633/Z/15/Z","098357/Z/12/Z","219478/Z/19/Z","092096","23363","MC_PC_17230","679411","25636"],"pubmed_authors":["Dabrowska C","Fink J","England F","Kim JK","Han S","Azzarelli R","Yum MK","Lee E","Trendafilova T","Koo BK","Pshenichnaya I","Philpott A","Stange DE","Chatzeli L","Simons BD","Wu SS","Mustata R","Lee JH"],"additional_accession":[]},"is_claimable":false,"name":"Tracing oncogene-driven remodelling of the intestinal stem cell niche.","description":"Interactions between tumour cells and the surrounding microenvironment contribute to tumour progression, metastasis and recurrence<sup>1-3</sup>. Although mosaic analyses in Drosophila have advanced our understanding of such interactions<sup>4,5</sup>, it has been difficult to engineer parallel approaches in vertebrates. Here we present an oncogene-associated, multicolour reporter mouse model-the Red2Onco system-that allows differential tracing of mutant and wild-type cells in the same tissue. By applying this system to the small intestine, we show that oncogene-expressing mutant crypts alter the cellular organization of neighbouring wild-type crypts, thereby driving accelerated clonal drift. Crypts that express oncogenic KRAS or PI3K secrete BMP ligands that suppress local stem cell activity, while changes in PDGFR<sup>lo</sup>CD81<sup>+</sup> stromal cells induced by crypts with oncogenic PI3K alter the WNT signalling environment. Together, these results show how oncogene-driven paracrine remodelling creates a niche environment that is detrimental to the maintenance of wild-type tissue, promoting field transformation dominated by oncogenic clones.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Jun","modification":"2025-04-04T02:26:06.717Z","creation":"2025-04-04T02:26:06.717Z"},"accession":"S-EPMC7614896","cross_references":{"pubmed":["34079126"],"doi":["10.1038/s41586-021-03605-0"]}}