Dichotomous ovarian cancer-initiating potential of Pax8+ cells revealed by a mouse genetic mosaic model.

ABSTRACT: 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 s

SUBMITTER: Zeng J 

PROVIDER: S-EPMC10189502 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature