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

doi:10.1016/j.celrep.2018.03.114

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

Cell Rep. 2018 Apr 24;23(4):1205-1219. doi: 10.1016/j.celrep.2018.03.114.

Authors

Affiliations

¹ Department of Biomedicine, University of Bergen, Bergen 5009, Norway; Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen 5009, Norway.
² Institute of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland.
³ Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
⁴ Department of Pathology and Laboratory Medicine, Center for Comparative Medicine, University of California, Davis, School of Medicine, Sacramento, CA, USA.
⁵ Department of Electrical and Biomedical Engineering, University of Nevada, Reno, NV, USA.
⁶ 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. Electronic address: mlabarge@coh.org.
⁷ Institute of Molecular Life Sciences, University of Zürich, 8057 Zürich, Switzerland. Electronic address: bernd.bodenmiller@imls.uzh.ch.
⁸ Department of Biomedicine, University of Bergen, Bergen 5009, Norway; Centre for Cancer Biomarkers (CCBIO), University of Bergen, Bergen 5009, Norway. Electronic address: jim.lorens@uib.no.

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.

Keywords: aging; breast cancer; heterogeneity; human mammary epithelia; mass cytometry; single-cell analysis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Aging / metabolism*
Female
Humans
Mammary Glands, Human / cytology*
Mammary Glands, Human / metabolism*
Middle Aged

Abstract

Publication types

MeSH terms

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