TY - JOUR
T1 - Aging-Associated Alterations in Mammary Epithelia and Stroma Revealed by Single-Cell RNA Sequencing
AU - Li, Carman Man Chung
AU - Shapiro, Hana
AU - Tsiobikas, Christina
AU - Selfors, Laura M.
AU - Chen, Huidong
AU - Rosenbluth, Jennifer
AU - Moore, Kaitlin
AU - Gupta, Kushali P.
AU - Gray, G. Kenneth
AU - Oren, Yaara
AU - Steinbaugh, Michael J.
AU - Guerriero, Jennifer L.
AU - Pinello, Luca
AU - Regev, Aviv
AU - Brugge, Joan S.
N1 - Publisher Copyright:
© 2020 The Author(s)
PY - 2020/12/29
Y1 - 2020/12/29
N2 - 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.
AB - 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.
KW - aging
KW - endothelial cells
KW - fibroblasts
KW - luminal and myoepithelial cells
KW - macrophages
KW - mammary epithelia and stroma
KW - single-cell RNA-seq
UR - http://www.scopus.com/inward/record.url?scp=85098645848&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2020.108566
DO - 10.1016/j.celrep.2020.108566
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C2 - 33378681
AN - SCOPUS:85098645848
SN - 2211-1247
VL - 33
JO - Cell Reports
JF - Cell Reports
IS - 13
M1 - 108566
ER -
