High-Dimensional Phenotyping Identifies Age-Emergent Cells in Human Mammary Epithelia.
Title | High-Dimensional Phenotyping Identifies Age-Emergent Cells in Human Mammary Epithelia. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Vatter FAPelissie, Schapiro D, Chang H, Borowsky AD, Lee JK, Parvin B, Stampfer MR, LaBarge MA, Bodenmiller B, Lorens JB |
Journal | Cell Rep |
Volume | 23 |
Issue | 4 |
Pagination | 1205-1219 |
Date Published | 2018 Apr 24 |
ISSN | 2211-1247 |
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. |
DOI | 10.1016/j.celrep.2018.03.114 |
Alternate Journal | Cell Rep |
PubMed ID | 29694896 |
PubMed Central ID | PMC5946804 |
Grant List | R00 AG033176 / AG / NIA NIH HHS / United States R01 AG040081 / AG / NIA NIH HHS / United States UC4 DK108132 / DK / NIDDK NIH HHS / United States |