High-Dimensional Phenotyping Identifies Age-Emergent Cells in Human Mammary Epithelia
Open accessAbstract
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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Accumulation of lumen and progenitor cells with age may lead to an increased risk of carcinogenesis.
“Vatter et al. [50] performed a phenotypic analysis of mammary epithelial cells from 57 women (16–91 years old) and showed that accumulation of lumen and progenitor cells with age may lead to an increased risk of carcinogenesis.”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [50]
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Defining breast epithelial cell types in the single-cell era
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Self-citationSupervised Machine Learning with CITRUS for Single Cell Biomarker Discovery
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A cellular identity crisis? Plasticity changes during aging and rejuvenationPreprint
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A Human Breast Cell Atlas Mapping the Homeostatic Cellular Shifts in the Adult BreastPreprint
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IL-1 and senescence: Friends and foe of EGFR neutralization and immunotherapy
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Deep proteome profiling of human mammary epithelia at lineage and age resolution
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Self-citationImmunosenescence: Molecular Mechanisms, Diseases, and Therapeutic Innovations
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Immunosenescence in skeletal muscle: The role-play in cancer cachexia chessboard
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Identification of a Proteomic Signature of Senescence in Primary Human Mammary Epithelial Cells
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Self-citationPregnancy Reduces Il33+ Hybrid Progenitor Accumulation in the Aged Mammary GlandPreprint
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Branching out: the diverse roles of stem and progenitor cells in mammary gland development
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- Authors
- Pelissier Vatter, F. A., Schapiro, D., Chang, H., Borowsky, A. D., Lee, J. K., Parvin, B., Stampfer, M. R., LaBarge, M. A., Bodenmiller, B., & Lorens, J. B.
- Affiliations
- University of Zurich (CH)
- Lawrence Berkeley National Laboratory (US)
- University of California Davis Medical Center (US)
- University of Nevada, Reno (US)
- City Of Hope National Medical Center (US)
- University of Bergen (NO)
- Corresponding author
- LaBarge, Mark A.
- Bodenmiller, Bernd
- Lorens, James B.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 23
- Issue
- 4
- Pages
- 1205-1219
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5946804
- OpenAlex
- W2801213376
- Cited by
- 58
- References
- 63
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 8 · 2023: 9 · 2022: 3 · 2021: 13 · 2020: 9 · 2019: 6 · 2018: 1
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc-nd)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- European Research Council
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (PP00P3-144874, 316030-139220, UC4 DK108132)
- Norges Forskningsråd (223250, 240130)
- Helse Vest (911794)
- National Institutes of Health (R00AG033176, R01AG040081, BC141351)
- Seventh Framework Programme (FP/2007-2013, 336921)
- Universitetet i Bergen
- Universität Zürich (FK-74419-01-01, BIOEF-17-001)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- mammary epithelium, aging, breast cancer susceptibility, epithelial progenitors, mass cytometry, population partitioning, tumor suppression
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Female, Humans, Middle Aged, Mammary Glands, Human
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