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

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

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2018

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Article

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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.

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Pelissier Vatter, F. A., Schapiro, D., Chang, H., Borowsky, A. D., Lee, J. K., Parvin, B., … Lorens, J. B. (2018). High-Dimensional Phenotyping Identifies Age-Emergent Cells in Human Mammary Epithelia. Cell Reports, 23(4), 1205–1219. doi:10.1016/j.celrep.2018.03.114

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2211-1247

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