Mass Cytometric Analysis Reveals Viable Activated Caspase-3+ Luminal Progenitors in the Normal Adult Human Mammary Gland

David J.H.F. Knapp, Nagarajan Kannan, Davide Pellacani, Connie J. Eaves

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The normal adult human female mammary gland is a bilayered structure consisting of an outer basal layer and two readily distinguished subsets of cells within the inner luminal layer. We now present a validated methodology for undertaking large-scale multi-parameter mass cytometric analyses of these cell types at single-cell resolution. In addition, we show how combining this approach with in vitro clonogenic assays of the proliferative and signaling responses of normal human mammary cells to epidermal growth factor (EGF) allows additional subsets with different EGF responses to be discerned. This included the identification of a subset of cells within the phenotypically defined luminal progenitor fraction that displays an elevated content of active caspase-3, including some that generate clones in vitro in response to EGF, with immunohistochemical evidence of their presence in situ in fixed preparations of normal human breast tissue. Knapp et al. identify a subpopulation of progenitors in the human mammary gland that have partially activated an apoptotic program despite retaining some viability and clonogenic potential. As such activation has been linked to genomic instability, these cells may be at increased risk for oncogenic transformation.

Original languageEnglish (US)
Pages (from-to)1116-1126
Number of pages11
JournalCell Reports
Volume21
Issue number4
DOIs
StatePublished - Oct 24 2017

Keywords

  • apoptosis
  • cancer
  • cell death
  • genomic instability
  • growth factors
  • mammary
  • mass cytometry
  • signaling
  • single-cell biology

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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