Diversity and heterogeneity in human breast cancer adipose tissue revealed at single-nucleus resolution

Frontiers in Immunology

Immunology

Lina Tang¹  Yanping Huo²  Jing Xie²  Tingting Li³ 

[1] Advanced Medical Research Center of Zhengzhou University, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China;Department of Breast Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China;Department of Cell Biology, Key Laboratory of Cell Biology, National Health Commission of the PRC and Key Laboratory of Medical Cell Biology, Ministry of Education of the PRC, China Medical University, Shenyang, Liaoning, China;

关键词: breast cancer;    adipose tissue;    single-cell RNA sequencing;    diversity;    heterogeneity;   

DOI  :  10.3389/fimmu.2023.1158027

 received in 2023-02-03, accepted in 2023-04-11,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionThere is increasing awareness of the role of adipose tissue in breast cancer occurrence and development, but no comparison of adipose adjacent to breast cancer tissues and adipose adjacent to normal breast tissues has been reported.MethodsSingle-nucleus RNA sequencing (snRNA-seq)was used to analyze cancer-adjacent and normal adipose tissues from the same breast cancer patient to characterize heterogeneity. SnRNA-seq was performed on 54513 cells from six samples of normal breast adipose tissue (N) distant from the tumor and tumor-adjacent adipose tissue (T) from the three patients (all surgically resected).Results and discussionSignificant diversity was detected in cell subgroups, differentiation status and, gene expression profiles. Breast cancer induces inflammatory gene profiles in most adipose cell types, such as macrophages, endothelial cells, and adipocytes. Furthermore, breast cancer decreased lipid uptake and the lipolytic phenotype and caused a switch to lipid biosynthesis and an inflammatory state in adipocytes. The in vivo trajectory of adipogenesis revealed distinct transcriptional stages. Breast cancer induced reprogramming across many cell types in breast cancer adipose tissues. Cellular remodeling was investigated by alterations in cell proportions, transcriptional profiles and cell-cell interactions. Breast cancer biology and novel biomarkers and therapy targets may be exposed.

【 授权许可】

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Copyright © 2023 Tang, Li, Xie and Huo