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
Affiliations
Fanny A. Pelissier Vatter
Department of Biomedicine, University of Bergen, Bergen 5009, Norway; Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen 5009, Norway
Denis Schapiro
Institute of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland
Hang Chang
Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA
Alexander D. Borowsky
Department of Pathology and Laboratory Medicine, Center for Comparative Medicine, University of California, Davis, School of Medicine, Sacramento, CA, USA
Jonathan K. Lee
Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA
Bahram Parvin
Department of Electrical and Biomedical Engineering, University of Nevada, Reno, NV, USA
Martha R. Stampfer
Institute of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland
Mark A. LaBarge
Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen 5009, Norway; Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; Department of Population Sciences & Center for Cancer and Aging, City of Hope, Duarte, CA, USA; Corresponding author
Bernd Bodenmiller
Institute of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland; Corresponding author
James B. Lorens
Department of Biomedicine, University of Bergen, Bergen 5009, Norway; Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen 5009, Norway; Corresponding author
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
