期刊
CELL REPORTS
卷 33, 期 13, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2020.108566
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资金
- Susan G. Komen postdoctoral fellowship
- Croucher postdoctoral fellowship
- NIH
- Hope Funds postdoctoral fellowship
- Marsha Rivkin Center for Ovarian Cancer Research
- Chan Zuckerberg Initiative DonorAdvised Fund [2018-182734]
- Silicon Valley Community Foundation
- NHGRI Career Development Award
- NHGRI Genome Innovator Award [R00HG008399, R35HG010717]
- Susan G. Komen Breast Cancer Foundation
- Breast Cancer Research Foundation
Aging is closely associated with increased susceptibility to breast cancer, yet there have been limited systematic studies of aging-induced alterations in the mammary gland. Here, we leverage high-throughput single-cell RNA sequencing to generate a detailed transcriptomic atlas of young and aged murine mammary tissues. By analyzing epithelial, stromal, and immune cells, we identify age-dependent alterations in cell proportions and gene expression, providing evidence that suggests alveolar maturation and physiological decline. The analysis also uncovers potential pro-tumorigenic mechanisms coupled to the age-associated loss of tumor suppressor function and change in microenvironment. In addition, we identify a rare, age-dependent luminal population co-expressing hormone-sensing and secretory-alveolar lineage markers, as well as two macrophage populations expressing distinct gene signatures, underscoring the complex heterogeneity of the mammary epithelia and stroma. Collectively, this rich single-cell atlas reveals the effects of aging on mammary physiology and can serve as a useful resource for understanding aging-associated cancer risk.
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