Single-cell RNA-Sequencing revealed an inflammaging phenotype in aged mouse mammary gland 4821

Abstract Description Population and epidemiology studies characterized age as the greatest risk factor for breast cancer incidence. While emerging evidence underscores the significance of stroma in tumor development, how aging rewires the mammary gland immune microenvironment remains largely unknown. Here, we performed a comprehensive single-cell transcriptome profiling of BALB/cJ female mice mammary gland across multiple postnatal development stages. In-depth analysis revealed an “inflammaging” phenotype in aged mammary gland. Specifically, in the myeloid compartment, we noted a reduction of M2 and an increase of pro-inflammatory monocyte-derived macrophages in aged mammary glands. In the lymphoid compartment, we observed a significant presence of ApoehighPlac8high B cells within aged tissue. While the puberty population was dominated by naïve and TCM cells, we found a shift towards a dysfunctional and memory-like population during aging. Notably, an exhausted Gzmk+CD8+ T population, a hallmark of inflammaging, was found exclusively in the aged mammary gland. In the context of murine mammary gland, we conducted a thorough examination of the aging impact on the cellular and transcriptomic landscape of the peripheral tissue immune populations. Prospectively, we will leverage the intercellular communication networks and intracellular gene regulatory networks to identify niche factors contributing to the inflammaging phenotypes and validate them with single-cell resolution spatial-transcriptomics. Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)