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. Single-cell RNA-seq (scRNA-seq) analysis of mammary tissues of 3 young mice (3-4 months of age) and 4 aged mice (13-14 months of age) using the 10X Chromium v2 platform.乳腺衰老与乳腺癌易感性升高密切相关，但目前针对该器官内衰老诱导的改变开展的系统性研究仍较为有限。本研究借助高通量单细胞RNA测序（single-cell RNA-sequencing, scRNA-seq）技术，构建了年轻与衰老小鼠乳腺组织的高精度转录组图谱，涵盖上皮细胞与基质细胞两大类群。分析发现，衰老可导致多种细胞群的比例发生改变，并出现独特的基因表达模式，且该现象与小鼠的妊娠史及激素周期无关。此外，本研究检测到一类罕见的腔细胞群，其同时表达激素感应与肺泡谱系标志物，并具备独特的基因表达特征；该细胞群的相对丰度随衰老进程显著降低。总体而言，这一高分辨率转录组图谱揭示了衰老对正常乳腺生理的影响，可为理解衰老相关的乳腺癌易感性提供宝贵的研究资源。本研究采用10X Chromium v2平台，对3只年轻小鼠（3~4月龄）与4只衰老小鼠（13~14月龄）的乳腺组织开展了单细胞RNA测序（scRNA-seq）分析。