| First Author | Zeng J | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 5 | Pages | 106742 |
| PubMed ID | 37207276 | Mgi Jnum | J:335835 |
| Mgi Id | MGI:7485387 | Doi | 10.1016/j.isci.2023.106742 |
| Citation | Zeng J, et al. (2023) Dichotomous ovarian cancer-initiating potential of Pax8+ cells revealed by a mouse genetic mosaic model. iScience 26(5):106742 |
| abstractText | Different cellular compartments within a tissue present distinct cancer-initiating capacities. Current approaches to dissect such heterogeneity require cell-type-specific genetic tools based on a well-understood lineage hierarchy, which are lacking for many tissues. Here, we circumvented this hurdle and revealed the dichotomous capacity of fallopian tube Pax8+ cells in initiating ovarian cancer, utilizing a mouse genetic system that stochastically generates rare GFP-labeled mutant cells. Through clonal analysis and spatial profiling, we determined that only clones founded by rare, stem/progenitor-like Pax8+ cells can expand on acquiring oncogenic mutations whereas vast majority of clones stall immediately. Furthermore, expanded mutant clones undergo further attrition: many turn quiescent shortly after the initial expansion, whereas others sustain proliferation and manifest a bias toward Pax8+ fate, underlying early pathogenesis. Our study showcases the power of genetic mosaic system-based clonal analysis for revealing cellular heterogeneity of cancer-initiating capacity in tissues with limited prior knowledge of lineage hierarchy. |
