Intraclonal plasticity in mammary tumors revealed through large-scale single-cell resolution 3D imaging
Details
Publication Year 2019-04-15, Volume 35, Issue #4, Page 618-632 e6
Journal Title
Cancer Cell
Publication Type
Journal Article
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.
Publisher
Cell Press
WEHI Research Division(s)
Cancer Biology And Stem Cells; Bioinformatics; Advanced Technology And Biology
PubMed ID
30930118
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2019-04-26 10:14:45
Last Modified: 2019-04-26 02:04:26
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