Aging-associated alterations in mammary epithelia and stroma revealed by single-cell RNA sequencing

Aging of the mammary gland is closely associated with increased susceptibility to breast cancer, yet there have been limited systematic studies of aging-induced alterations within this organ. Here we leveraged the power of high-throughput single-cell RNA-sequencing (scRNA-seq) to generate a detailed transcriptomic atlas of young and aged murine mammary tissues, including both epithelial and stromal cell types. This analysis identified altered proportions and distinct gene expression patterns in multiple cell populations as a consequence of aging, independent of history of pregnancy and hormone cycle. In addition, we detected a rare luminal cell type that expresses both hormone-sensing and alveolar lineage markers as well as a unique gene expression signature. In addition, these cells exhibit a significant decrease in relative abundance with age. Overall, this high-resolution transcriptomic landscape reveals the effects of aging on normal mammary gland physiology and can serve as a valuable resource for understanding aging-associated susceptibility to breast cancer.