Related Experiment Video For Adipose microenvironment
Updated: May 12, 2026
Modeling Breast Cancer in Human Breast Tissue using a Microphysiological System
Published on: April 23, 2021
Single-Cell and Single-Nuclei transcriptomics profiling reveals dynamic cellular features in tumor-related adipose
Xiaoxiao Hu1, Fang Jia1, Lili Li2
1Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang, China; Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China.
Objectives:
High body mass index (BMI), encompassing overweight and obesity, is a well-established risk factor for developing breast cancer (BC). The underlying mechanisms linking elevated BMI to increased BC risk involve metabolic reprogramming and chronic inflammatory microenvironments regulated by cellular networks within breast white adipose tissue (WAT). However, the complicated landscape and specific cell chat leading to BC-related adipose microenvironment remained unclear.
Materials And Methods:
We unveiled a comprehensive cell atlas by employing single-cell (N = 27) and single-nuclei (N = 6) transcriptomics to address dynamic changes of immune and stromal cell components within WAT in high BMI population. Bulk RNA-seq data sets were used for validation.
Results:
Characteristics of adipose-infiltrating tissue-resident macrophages (PVMs), APOD+γδ T cells, and mature FKBP5+ adipocytes in breast cancer women with high BMI were revealed, in terms of transcriptional genes, metabolism features, developmental trajectories and gene set enrichment analysis (GSEA). PVMs upregulated c-Maf combined with its co-activator CREB1 to increase TCA cycles. APOD+γδ T cells were found to elevate intracellular lipid metabolism, leading to poor clinical prognosis. Mature FKBP5+adipocytes served as an advanced adipogenesis mediator to promote tumor aggressiveness. In-depth analysis of cell-cell interactions uncovered a remodeling trend towards metabolic dysfunction and chronic inflammation in WAT with weight gain via EGF, CXCL, and CCL signalings.
Conclusion:
These results provided a novel understanding of detailed and unbiased cellular landscape of WAT in breast cancer with high BMI from single-cell atlas perspective, uncovering interplays between breast adipose-infiltrating immune cells and stromal cells that promote progression of BC under high BMI conditions.
