Aging-Associated Alterations in Mammary Epithelia and Stroma Revealed by Single-Cell RNA Sequencing
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1-s2.0-S2211124720315552-main.pdf
Description
Published version
Size
9.91 MB
Format
Adobe PDF
Checksum (MD5)
7ad8145ce1424b0daa42064e15627471
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
Date Issued
2020
Journal
Cell Reports
Publisher
Elsevier BV
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2020.108566
