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 language | English (US) |
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Pages (from-to) | 1116-1126 |
Number of pages | 11 |
Journal | Cell reports |
Volume | 21 |
Issue number | 4 |
DOIs | |
State | Published - Oct 24 2017 |
Keywords
- apoptosis
- cancer
- cell death
- genomic instability
- growth factors
- mammary
- mass cytometry
- signaling
- single-cell biology
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology