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Intraclonal Plasticity in Mammary Tumors Revealed through Large-Scale Single-Cell Resolution 3D Imaging.
- Source :
-
Cancer Cell . Apr2019, Vol. 35 Issue 4, p618-618. 1p. - Publication Year :
- 2019
-
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. • A single-step, non-toxic clearing agent for 3D imaging of whole organs and tumors • Derivation of an integrative platform to interrogate intratumoral heterogeneity • Profound clonal restriction occurs during neoplastic progression • The epithelial-mesenchymal transition occurs clonally as a frequent event Rios et al. develop a rapid, large-scale single-cell resolution 3D imaging protocol and use the protocol together with RNA sequencing to explore the cellular dynamics of mammary tumorigenesis and show that a molecular epithelial-to-mesenchymal transition is a prominent feature of tumor clones. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15356108
- Volume :
- 35
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Cancer Cell
- Publication Type :
- Academic Journal
- Accession number :
- 136072398
- Full Text :
- https://doi.org/10.1016/j.ccell.2019.02.010