Table_2_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发展中的作用认知不断深化，但目前尚无针对乳腺癌组织邻近脂肪组织与肿瘤远端正常乳腺脂肪组织的对比研究报道。方法 本研究采用单细胞核RNA测序（single-nucleus RNA sequencing, snRNA-seq）技术，对乳腺癌患者的癌旁脂肪组织与正常脂肪组织进行分析，以解析其异质性。本研究共纳入3名患者的6份手术切除组织样本，其中3份为肿瘤远端的正常乳腺脂肪组织（标记为N），剩余3份为癌旁脂肪组织（标记为T），最终对共计54513个细胞完成snRNA-seq测序。结果与讨论 研究在细胞亚群、分化状态及基因表达谱中均检测到显著差异。乳腺癌可在巨噬细胞、内皮细胞、脂肪细胞等多数脂肪组织细胞类型中诱导炎症相关基因表达谱的形成。此外，乳腺癌会降低脂肪细胞的脂质摄取能力与脂解表型，促使其转向脂质生物合成及炎症状态。体内脂肪生成轨迹呈现出不同的转录阶段。乳腺癌可诱导乳腺癌相关脂肪组织内多种细胞类型发生重编程。本研究通过细胞比例变化、转录谱改变以及细胞间相互作用，对细胞重塑过程进行了分析。本研究或可揭示乳腺癌的生物学特性、新型生物标志物以及潜在治疗靶点。