| First Author | Yum MK | Year | 2021 |
| Journal | Nature | Volume | 594 |
| Issue | 7863 | Pages | 442-447 |
| PubMed ID | 34079126 | Mgi Jnum | J:322623 |
| Mgi Id | MGI:7259781 | Doi | 10.1038/s41586-021-03605-0 |
| Citation | Yum MK, et al. (2021) Tracing oncogene-driven remodelling of the intestinal stem cell niche. Nature 594(7863):442-447 |
| abstractText | Interactions between tumour cells and the surrounding microenvironment contribute to tumour progression, metastasis and recurrence1-3. Although mosaic analyses in Drosophila have advanced our understanding of such interactions4,5, 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 PDGFRloCD81+ 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. |
