Your browser doesn't support javascript.
loading
Intraclonal Plasticity in Mammary Tumors Revealed through Large-Scale Single-Cell Resolution 3D Imaging.
Rios, Anne C; Capaldo, Bianca D; Vaillant, François; Pal, Bhupinder; van Ineveld, Ravian; Dawson, Caleb A; Chen, Yunshun; Nolan, Emma; Fu, Nai Yang; Jackling, Felicity C; Devi, Sapna; Clouston, David; Whitehead, Lachlan; Smyth, Gordon K; Mueller, Scott N; Lindeman, Geoffrey J; Visvader, Jane E.
Affiliation
  • Rios AC; Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The
  • Capaldo BD; Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Vaillant F; Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Pal B; Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • van Ineveld R; Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.
  • Dawson CA; Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Chen Y; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia; Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Nolan E; Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Fu NY; Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Jackling FC; Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Devi S; Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3050, Australia; The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Melbourne, VIC 3000, Australia.
  • Clouston D; TissuPATH, Melbourne, VIC 3149, Australia.
  • Whitehead L; Centre for Dynamic Imaging, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • Smyth GK; Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; School of Mathematics and Statistics, The University of Melbourne, Parkville, VIC 3010, Australia.
  • Mueller SN; Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3050, Australia; The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Melbourne, VIC 3000, Australia.
  • Lindeman GJ; Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Oncology, The Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia; Department of Medicine, The University of Melbourne, Parkville, VIC 3010, Austra
  • Visvader JE; Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: visvader@wehi.edu.au.
Cancer Cell ; 35(4): 618-632.e6, 2019 04 15.
Article in En | MEDLINE | ID: mdl-30930118
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.
Subject(s)
Key words
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Breast Neoplasms / Microscopy, Confocal / Cell Lineage / Imaging, Three-Dimensional / Single-Cell Analysis / Epithelial-Mesenchymal Transition / Cell Plasticity Limits: Animals / Female / Humans Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2019 Document type: Article
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Breast Neoplasms / Microscopy, Confocal / Cell Lineage / Imaging, Three-Dimensional / Single-Cell Analysis / Epithelial-Mesenchymal Transition / Cell Plasticity Limits: Animals / Female / Humans Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2019 Document type: Article