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Intraclonal plasticity in mammary tumors revealed through large-scale single-cell resolution 3D imaging


Rios, AC; Capaldo, BD; Vaillant, F; Pal, B; van Ineveld, R; Dawson, CA; Chen, Y; Nolan, E; Fu, NY; 3DTCLSM Group,; Jackling, FC; Devi, S; Clouston, D; Whitehead, L; Smyth, GK; Mueller, SN; Lindeman, GJ; Visvader, JE
2019-04-15
Cancer Cell
Journal Article
35
4
618-632 e6
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.
Cell Press
Cancer Biology and Stem Cells; Bioinformatics; Advanced Technology and Biology
10.1016/j.ccell.2019.02.010
30930118
Refer to article for additional funding acknowledgements
Refer to copyright notice on published article.

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