期刊
CELL REPORTS
卷 23, 期 4, 页码 1205-1219出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.03.114
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资金
- University of Bergen
- Forschungskredit of the University of Zurich [FK-74419-01-01]
- BioEntrepreneur-Fellowship of the University of Zurich [BIOEF-17-001]
- Research Council of Norway [240130]
- Centres of Excellence funding scheme [223250]
- Helse Vest Health Authority [911794]
- NIH [R00AG033176, R01AG040081]
- Congressionally Directed Medical Research Programs Breast Cancer Research Program Era of Hope Scholar Award [BC141351]
- Swiss National Science Foundation (SNSF) R'Equip grant [316030-139220]
- SNSF [PP00P3-144874]
- PhosphonetPPM SystemsX grant [UC4 DK108132]
- European Research Council (ERC) under the European Union's Seventh Framework Programme (FP)/ERC Grant [336921]
- Forschungskredit Fellowship of the University of Zurich
- Swiss National Science Foundation (SNF) [316030_139220] Funding Source: Swiss National Science Foundation (SNF)
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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