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

3DTCLSM Group

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107 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)618-632.e6
JournalCancer Cell
Volume35
Issue number4
DOIs
Publication statusPublished - 15 Apr 2019

Keywords

  • 3D imaging
  • breast cancer
  • cell-of-origin
  • clonal competition
  • Elf5
  • EMT
  • lineage tracing
  • luminal progenitor
  • plasticity
  • tumor suppressor

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