Intraclonal Plasticity in Mammary Tumors Revealed through Large-Scale Single-Cell Resolution 3D Imaging Academic Article uri icon

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.

authors

  • 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

publication date

  • 2019

has subject area