研究动态
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单细胞RNA揭示人类乳腺肿瘤界面区域中的肿瘤生成微环境。

Single-cell RNA reveals a tumorigenic microenvironment in the interface zone of human breast tumors.

发表日期:2023 Aug 29
作者: Wei Yang, Meiyu Xu, Shuoqi Xu, Qingxian Guan, Shuaiming Geng, Juanhong Wang, Wei Wei, Hongwei Xu, Ying Liu, Yong Meng, Ming-Qing Gao
来源: Stem Cell Research & Therapy

摘要:

界面区域,即浸润性癌附近的区域,可以看作是存在肿瘤入侵前变化的肿瘤微环境的实际组织。然而,界面区域微环境的异质性和特征尚未被彻底探索。对于体外研究,我们使用单细胞RNA测序(scRNA-seq)对肿瘤区域、正常区域和界面区域的细胞进行了表征,其中肿瘤浸润前缘与正常区域之间有5毫米宽的带状区域。通过scRNA-seq数据分析,我们比较了不同区域中的细胞类型及其转录特征。进行了伪时间、细胞间通讯和通路分析以表征区域特异的微环境。细胞增殖、伤口愈合和克隆形成实验探究了差异表达基因BMPR1B的功能,这在体内肿瘤模型中得到了确认。 筛选后,获得并确定了88,548个高质量的细胞。调节性T细胞、M2巨噬细胞、与血管生成相关的肥大细胞、DNA修复能力较弱的干细胞、具有血管生成活性的内皮细胞、合成胶原的成纤维细胞以及具有增殖活性的上皮细胞在界面区域形成了独特的肿瘤微环境。细胞间通讯分析揭示了界面区域不同细胞类型之间存在特殊的配体-受体对,这与正常区域相比,保护了内皮细胞的凋亡,并促进了上皮细胞的增殖和迁移。与正常区域相比,高表达的BMPR1B基因促进了界面区域癌细胞的肿瘤生成能力。 我们的研究鉴定了界面区域独特的肿瘤微环境,深入洞察了乳腺癌肿瘤微环境,将为促进乳腺癌诊断和治疗提供有益的资源。© 2023. BioMed Central Ltd., part of Springer Nature.
The interface zone, area around invasive carcinoma, can be thought of as the actual tissue of the tumor microenvironment with precedent alterations for tumor invasion. However, the heterogeneity and characteristics of the microenvironment in the interface area have not yet been thoroughly explored.For in vitro studies, single-cell RNA sequencing (scRNA-seq) was used to characterize the cells from the tumor zone, the normal zone and the interface zone with 5-mm-wide belts between the tumor invasion front and the normal zone. Through scRNA-seq data analysis, we compared the cell types and their transcriptional characteristics in the different zones. Pseudotime, cell-cell communication and pathway analysis were performed to characterize the zone-specific microenvironment. Cell proliferation, wound healing and clone formation experiments explored the function of differentially expressed gene BMPR1B, which were confirmed by tumor models in vivo.After screening, 88,548 high-quality cells were obtained and identified. Regulatory T cells, M2 macrophages, angiogenesis-related mast cells, stem cells with weak DNA repair ability, endothelial cells with angiogenic activity, fibroblasts with collagen synthesis and epithelial cells with proliferative activity form a unique tumorigenic microenvironment in the interface zone. Cell-cell communication analysis revealed that there are special ligand-receptor pairs between different cell types in the interface zone, which protects endothelial cell apoptosis and promotes epithelial cell proliferation and migration, compared to the normal zone. Compared with the normal zone, the highly expressed BMPR1B gene promotes the tumorigenic ability of cancer cells in the interface zone.Our work identified a unique tumorigenic microenvironment of the interface zone and allowed for deeper insights into the tumor microenvironment of breast cancer that will serve as a helpful resource for advancing breast cancer diagnosis and therapy.© 2023. BioMed Central Ltd., part of Springer Nature.