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

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalCell Reports
DOIs
StateAccepted/In press - Jan 1 2018

Keywords

  • aging
  • breast cancer
  • heterogeneity
  • human mammary epithelia
  • mass cytometry
  • single-cell analysis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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