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

Carman Man Chung Li, Hana Shapiro, Christina Tsiobikas, Laura M. Selfors, Huidong Chen, Jennifer Rosenbluth, Kaitlin Moore, Kushali P. Gupta, G. Kenneth Gray, Yaara Oren, Michael J. Steinbaugh, Jennifer L. Guerriero, Luca Pinello, Aviv Regev, Joan S. Brugge

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number108566
JournalCell Reports
Volume33
Issue number13
DOIs
StatePublished - 29 Dec 2020
Externally publishedYes

Keywords

  • aging
  • endothelial cells
  • fibroblasts
  • luminal and myoepithelial cells
  • macrophages
  • mammary epithelia and stroma
  • single-cell RNA-seq

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