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High-Dimensional Phenotyping Identifies Age-Emergent Cells in Human Mammary Epithelia
Author(s) -
Fanny A. Pelissier Vatter,
Denis Schapiro,
Hang Chang,
Alexander D. Borowsky,
Jonathan Lee,
Bahram Parvin,
Martha R. Stampfer,
Mark A. LaBarge,
Bernd Bodenmiller,
James B. Lorens
Publication year - 2018
Publication title -
cell reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.264
H-Index - 154
eISSN - 2639-1856
pISSN - 2211-1247
DOI - 10.1016/j.celrep.2018.03.114
Subject(s) - biology , progenitor cell , phenotype , breast cancer , basal (medicine) , population , cell , mammary gland , epithelium , cell type , flow cytometry , microbiology and biotechnology , stem cell , cancer , immunology , genetics , endocrinology , medicine , gene , environmental health , insulin
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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