Intraclonal plasticity in mammary tumors revealed through large-scale single-cell resolution 3D imaging
- Author(s)
- 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;
- 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
- Research Division(s)
- Cancer Biology And Stem Cells; Bioinformatics; Advanced Technology And Biology
- PubMed ID
- 30930118
- Publisher's Version
- https://doi.org/10.1016/j.ccell.2019.02.010
- NHMRC Grants
- NHMRC/461221, NHMRC/1016701, NHMRC/1024852, NHMRC/1054618, NHMRC/1042629, NHMRC/490037, NHMRC/637307, NHMRC/1037230, NHMRC/1102742,
- Terms of Use/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