Comprehensive single-cell aging atlas of healthy mammary tissues reveals shared epigenomic and transcriptomic signatures of aging and cancer
Aging is the greatest risk factor for breast cancer; however, how age-related cellular and molecular events impact cancer initiation is unknown. In this study, we investigated how aging rewires transcriptomic and epigenomic programs of mouse mammary glands at single-cell resolution, yielding a comprehensive resource for aging and cancer biology. Aged epithelial cells exhibit epigenetic and transcriptional changes in metabolic, pro-inflammatory and cancer-associated genes. Aged stromal cells downregulate fibroblast marker genes and upregulate markers of senescence and cancer-associated fibroblasts. Among immune cells, distinct T cell subsets (Gzmk<sup>+</sup>, memory CD4<sup>+</sup>, γδ) and M2-like macrophages expand with age. Spatial transcriptomics reveals co-localization of aged immune and epithelial cells in situ. Lastly, we found transcriptional signatures of aging mammary cells in human breast tumors, suggesting possible links between aging and cancer. Together, these data uncover that epithelial, immune and stromal cells shift in proportions and cell identity, potentially impacting cell plasticity, aged microenvironment and neoplasia risk.
Authors
- Neerja Katiyar
- Mark A. LaBarge (ORCID: https://orcid.org/0000-0003-2405-4719)
- Hyeon Gu Kang (ORCID: https://orcid.org/0000-0002-5822-6825)
- Djamel Nehar-Belaid (ORCID: https://orcid.org/0000-0001-6002-5021)
- Olga Anczuków (ORCID: https://orcid.org/0000-0003-0516-2677)
- Brittany Angarola (ORCID: https://orcid.org/0000-0001-8320-6781)
- Karolina Palucka (ORCID: https://orcid.org/0000-0002-1600-6066)
- Ron Korstanje (ORCID: https://orcid.org/0000-0002-2808-1610)
- Jeffrey H. Chuang (ORCID: https://orcid.org/0000-0002-3298-2358)
- Duygu Ucar (ORCID: https://orcid.org/0000-0002-9772-3066)
- Giray Naim Eryilmaz
- Rachel Gott
- Sung‐Hee Park
- Siddhartha Sharma (ORCID: https://orcid.org/0000-0002-8799-388X)
Institutions
- City of Hope (US)
- Jackson Laboratory (US)
- Beckman Research Institute
- UConn Health (US)
Publication Details
- Journal
- Nature Aging
- Published
- 2024-11-25
- DOI
- https://doi.org/10.1038/s43587-024-00751-8
- Citations
- 37
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 8.65
Funders
- National Institutes of Health
- U.S. National Library of Medicine