Cell Reports (Apr 2018)

High-Dimensional Phenotyping Identifies Age-Emergent Cells in Human Mammary Epithelia

  • Fanny A. Pelissier Vatter,
  • Denis Schapiro,
  • Hang Chang,
  • Alexander D. Borowsky,
  • Jonathan K. Lee,
  • Bahram Parvin,
  • Martha R. Stampfer,
  • Mark A. LaBarge,
  • Bernd Bodenmiller,
  • James B. Lorens

Journal volume & issue
Vol. 23, no. 4
pp. 1205 – 1219

Abstract

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Summary: Aging is associated with tissue-level changes in cellular composition that are correlated with increased susceptibility to disease. Aging human mammary tissue shows skewed progenitor cell potency, resulting in diminished tumor-suppressive cell types and the accumulation of defective epithelial progenitors. Quantitative characterization of these age-emergent human cell subpopulations is lacking, impeding our understanding of the relationship between age and cancer susceptibility. We conducted single-cell resolution proteomic phenotyping of healthy breast epithelia from 57 women, aged 16–91 years, using mass cytometry. Remarkable heterogeneity was quantified within the two mammary epithelial lineages. Population partitioning identified a subset of aberrant basal-like luminal cells that accumulate with age and originate from age-altered progenitors. Quantification of age-emergent phenotypes enabled robust classification of breast tissues by age in healthy women. This high-resolution mapping highlighted specific epithelial subpopulations that change with age in a manner consistent with increased susceptibility to breast cancer. : Vatter et al. find that single-cell mass cytometry of human mammary epithelial cells from 57 women, from 16 to 91 years old, depicts an in-depth phenotyping of aging mammary epithelia. Subpopulations of altered luminal and progenitor cells that accumulate with age may be at increased risk for oncogenic transformation. Keywords: human mammary epithelia, aging, mass cytometry, single-cell analysis, heterogeneity, breast cancer