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Aging-Associated Alterations in Mammary Epithelia and Stroma Revealed by Single-Cell RNA Sequencing

Author(s)
Li, Carman Man-Chung; Shapiro, Hana; Tsiobikas, Christina; Selfors, Laura M; Chen, Huidong; Rosenbluth, Jennifer; Moore, Kaitlin; Gupta, Kushali P; Gray, G Kenneth; Oren, Yaara; Steinbaugh, Michael J; Guerriero, Jennifer L; Pinello, Luca; Regev, Aviv; Brugge, Joan S; ... Show more Show less
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Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/
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Abstract
© 2020 The Author(s) 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.
Date issued
2020
URI
https://hdl.handle.net/1721.1/136089
Department
Massachusetts Institute of Technology. Department of Biology
Journal
Cell Reports
Publisher
Elsevier BV

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