单细胞和单核转录组学分析揭示了高BMI乳腺癌患者肿瘤相关脂肪微环境的动态细胞特征

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-05-10 DOI:10.1016/j.tranon.2025.102408

Xiaoxiao Hu , Fang Jia , Lili Li , Wuzhen Chen , Leyi Zhang , Jun Pan , Sangsang Zhu , Zhen Wang , Jian Huang

{"title":"单细胞和单核转录组学分析揭示了高BMI乳腺癌患者肿瘤相关脂肪微环境的动态细胞特征","authors":"Xiaoxiao Hu , Fang Jia , Lili Li , Wuzhen Chen , Leyi Zhang , Jun Pan , Sangsang Zhu , Zhen Wang , Jian Huang","doi":"10.1016/j.tranon.2025.102408","DOIUrl":null,"url":null,"abstract":"<div><h3>Objectives</h3><div>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.</div></div><div><h3>Materials and methods</h3><div>We unveiled a comprehensive cell atlas by employing single-cell (<em>N</em> = 27) and single-nuclei (<em>N</em> = 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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"57 ","pages":"Article 102408"},"PeriodicalIF":5.0000,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Single-Cell and Single-Nuclei transcriptomics profiling reveals dynamic cellular features in tumor-related adipose microenvironment of breast cancer patients with high BMI\",\"authors\":\"Xiaoxiao Hu , Fang Jia , Lili Li , Wuzhen Chen , Leyi Zhang , Jun Pan , Sangsang Zhu , Zhen Wang , Jian Huang\",\"doi\":\"10.1016/j.tranon.2025.102408\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objectives</h3><div>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.</div></div><div><h3>Materials and methods</h3><div>We unveiled a comprehensive cell atlas by employing single-cell (<em>N</em> = 27) and single-nuclei (<em>N</em> = 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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>\",\"PeriodicalId\":48975,\"journal\":{\"name\":\"Translational Oncology\",\"volume\":\"57 \",\"pages\":\"Article 102408\"},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2025-05-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1936523325001391\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1936523325001391","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

摘要

高体重指数（BMI），包括超重和肥胖，是发展乳腺癌（BC）的一个公认的危险因素。BMI升高与BC风险增加之间的潜在机制涉及代谢重编程和乳房白色脂肪组织（WAT）内细胞网络调节的慢性炎症微环境。然而，导致bc相关脂肪微环境的复杂景观和特定细胞聊天仍不清楚。材料和方法我们利用单细胞（N = 27）和单核（N = 6）转录组学研究了高BMI人群WAT中免疫和基质细胞成分的动态变化，从而建立了一个全面的细胞图谱。大量RNA-seq数据集用于验证。结果揭示了高BMI乳腺癌女性脂肪浸润组织内巨噬细胞（pvm）、APOD+γδ T细胞和成熟FKBP5+脂肪细胞在转录基因、代谢特征、发育轨迹和基因集富集分析（GSEA）等方面的特征。pvm上调c-Maf及其共激活剂CREB1以增加TCA周期。APOD+γδ T细胞升高细胞内脂质代谢，导致临床预后不良。成熟的FKBP5+脂肪细胞可作为促进肿瘤侵袭性的高级脂肪形成介质。对细胞间相互作用的深入分析揭示了通过EGF、CXCL和CCL信号在体重增加的WAT中代谢功能障碍和慢性炎症的重塑趋势。结论这些结果从单细胞图谱的角度对高BMI乳腺癌WAT的详细和公正的细胞景观提供了新的认识，揭示了高BMI条件下乳腺脂肪浸润性免疫细胞和基质细胞之间的相互作用，促进了BC的进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Single-Cell and Single-Nuclei transcriptomics profiling reveals dynamic cellular features in tumor-related adipose microenvironment of breast cancer patients with high BMI

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.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.