Table_4_Diversity and heterogeneity in human breast cancer adipose tissue revealed at single-nucleus resolution.xls

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.

引言 目前学界对脂肪组织在乳腺癌发生与进展中的作用认知日益深入，但尚未有针对乳腺癌组织毗邻脂肪与正常乳腺毗邻脂肪的对比研究报道。
方法 本研究采用单细胞核RNA测序（single-nucleus RNA sequencing, snRNA-seq）技术，对同一乳腺癌患者的癌旁脂肪组织与正常乳腺脂肪组织进行分析，以解析其异质性。研究共纳入3例乳腺癌患者的6份手术切除样本，分别为远离肿瘤的正常乳腺脂肪组织（标记为N组）与癌旁脂肪组织（标记为T组），总计对54513个细胞完成snRNA-seq检测。
结果与讨论 本研究在细胞亚群、分化状态及基因表达谱中均检测到显著异质性。乳腺癌可在多数脂肪组织细胞类型（如巨噬细胞、内皮细胞及脂肪细胞）中诱导炎症相关基因表达谱的激活。进一步研究发现，乳腺癌可降低脂肪细胞的脂质摄取能力与脂解表型，并促使其转向脂质生物合成及炎症状态。体内脂肪生成轨迹展现出特征鲜明的转录阶段。乳腺癌可诱导乳腺癌相关脂肪组织中多种细胞类型发生重编程。本研究通过细胞比例变化、转录谱特征及细胞间相互作用的改变，解析了细胞重塑过程，或可为揭示乳腺癌生物学特性、发掘新型生物标志物及治疗靶点提供重要依据。