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

High-Dimensional Phenotyping Identifies Age-Emergent Cells in Human Mammary Epithelia.
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DOI:
10.1016/j.celrep.2018.03.114
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发表时间:
2018-04-24
期刊:
影响因子:
8.8
通讯作者:
Lorens JB
Lorens JB
中科院分区:
生物学1区
文献类型:
--
作者:
Pelissier Vatter FA;Schapiro D;Chang H;Borowsky AD;Lee JK;Parvin B;Stampfer MR;LaBarge MA;Bodenmiller B;Lorens JB

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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. CyTOF analysis reveals human mammary epithelial heterogeneity with age Age-emergent luminal cells share phenotypes with candidate breast cancer cells of origin Classification models correctly assign tissue samples to their age group Age-related changes are conserved between mammary epithelial tissue and primary cells Vatter et al. find that single-cell mass cytometry of human mammary epithelial cells from 57 women, from 16 to 91 years old, depicts an in-depth phenotyping of aging mammary epithelia. Subpopulations of altered luminal and progenitor cells that accumulate with age may be at increased risk for oncogenic transformation.
年龄和绕过停滞的手段会影响永生的人类乳腺上皮细胞的内在亚型。
DOI: 10.3389/fcell.2015.00013
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