Single-Cell RNA-seq Reveals Obesity-Induced Alterations in the BRAC1 Mutant Mammary Tumor Microenvironment
In this study, we conducted single-cell RNA sequencing (scRNA-seq) studies to investigate the impact of high-fat diet (HFD)-induced obesity on transcriptomic landscapes of stromal and immune cells in mammary glands of Brca1-/-;p53+/- mice, an animal breast cancer model. The scRNA-seq profiling data showed that five different subtypes of stromal fibroblasts existed in mouse mammary glands. HFD-induced obesity led to upregulated expression of extracellular matrix (ECM) genes (Col3a1, Col6a3, Eln, and Sparc) and downregulated expression of immunoregulatory genes (Iigp1, Ccl2, and Cxcl10) in these stromal subtype cells. These findings, taken together, suggest that obesity alters the ECM composition and immune ecosystem through modulating the functionality of mammary stromal cells. Moreover, scRNA-seq analysis of mammary immune cells indicated that HFD-induced obesity promoted the generation and/or recruiting of pro-tumorigenic M2 macrophages in mammary glands. Overall design: Single-cell RNA-seq profiling analysis of stromal and immune cells in mammary glands isolated from either normal or obese C57BL6 Brca1-/-;p53+/- mice.