Identification of a Proteomic Signature of Senescence in Primary Human Mammary Epithelial Cells
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Abstract
Abstract Senescence is a permanent cell cycle arrest that occurs in response to cellular stress. Because senescent cells promote age-related disease, there has been considerable interest in defining the proteomic alterations in senescent cells. Because senescence differs greatly depending on cell type and senescence inducer, continued progress in the characterization of senescent cells is needed. Here, we analyzed primary human mammary epithelial cells (HMECs), a model system for aging, using mass spectrometry-based proteomics. By integrating data from replicative senescence, immortalization by telomerase reactivation, and drug-induced senescence, we identified a robust proteomic signature of HMEC senescence consisting of 77 upregulated and 36 downregulated proteins. This approach identified known biomarkers, such as downregulation of the nuclear lamina protein lamin-B1 (LMNB1), and novel upregulated proteins including the β-galactoside-binding protein galectin-7 (LGALS7). Gene ontology enrichment analysis demonstrated that senescent HMECs upregulated lysosomal proteins and downregulated RNA metabolic processes. We additionally integrated our proteomic signature of senescence with transcriptomic data from senescent HMECs to demonstrate that our proteomic signature can discriminate proliferating and senescent HMECs even at the transcriptional level. Taken together, our results demonstrate the power of proteomics to identify cell type-specific signatures of senescence and advance the understanding of senescence in primary HMECs.
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Flagged first, then by citations
- Authors
- Delfarah, A., Hartel, N. G., Zheng, D., Yang, J., & Graham, N. A.
- Affiliations
- University of Southern California (US)
- Corresponding author
- Graham, Nicholas A.
- Venue
- Journal of Proteome Research
- Publisher
- American Chemical Society (ACS)
- Published
- 2021-10-12
- Volume
- 20
- Issue
- 11
- Pages
- 5169-5179
- ISSN
- 1535-3893 (ISSN-L)
- 1535-3907
- OpenAlex
- W3105792631
- Cited by
- 8
- References
- 23
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 2 · 2022: 2
- FWCI
- 1.10
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Journal of Proteome Research (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- American Association for Cancer Research (20-80-44-GRAH)
- Rose Hills Foundation
- USC Provost's Office
- Viterbi School of Engineering
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- cellular senescence, proteomic signatures, human mammary epithelial cells, replicative senescence, telomerase reactivation, drug-induced senescence, lamin B1, galectin-7, lysosomal proteins, RNA metabolism, senescence biomarkers, transcriptome integration, aging
- MeSH terms
- Breast, Epithelial Cells, Humans, Cellular Senescence, Telomerase, Proteomics
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