| Literature DB >> 30930118 |
Anne C Rios1, Bianca D Capaldo2, François Vaillant2, Bhupinder Pal2, Ravian van Ineveld3, Caleb A Dawson2, Yunshun Chen4, Emma Nolan2, Nai Yang Fu2, Felicity C Jackling2, Sapna Devi5, David Clouston6, Lachlan Whitehead7, Gordon K Smyth8, Scott N Mueller5, Geoffrey J Lindeman9, Jane E Visvader10.
Abstract
Breast tumors are inherently heterogeneous, but the evolving cellular organization through neoplastic progression is poorly understood. Here we report a rapid, large-scale single-cell resolution 3D imaging protocol based on a one-step clearing agent that allows visualization of normal tissue architecture and entire tumors at cellular resolution. Imaging of multicolor lineage-tracing models of breast cancer targeted to either basal or luminal progenitor cells revealed profound clonal restriction during progression. Expression profiling of clones arising in Pten/Trp53-deficient tumors identified distinct molecular signatures. Strikingly, most clones harbored cells that had undergone an epithelial-to-mesenchymal transition, indicating widespread, inherent plasticity. Hence, an integrative pipeline that combines lineage tracing, 3D imaging, and clonal RNA sequencing technologies offers a comprehensive path for studying mechanisms underlying heterogeneity in whole tumors.Entities:
Keywords: 3D imaging; EMT; Elf5; breast cancer; cell-of-origin; clonal competition; lineage tracing; luminal progenitor; plasticity; tumor suppressor
Year: 2019 PMID： 30930118 DOI： 10.1016/j.ccell.2019.02.010
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743