■肾细胞癌(RCC)的特征在于其异质性及其肿瘤微环境的复杂性。这项研究解决了在细胞水平上理解RCC的需要,重点关注其三种主要亚型:透明细胞(ccRCC),发色(chRCC),和乳头状肾细胞癌(pRCC)。
■本研究旨在使用scRNA-seq技术全面表征RCC亚型的细胞多样性和细胞间通讯网络。通过关注巨噬细胞和癌症相关成纤维细胞(CAFs),我们试图揭示它们的功能状态,发展轨迹,和信号通路。
■我们利用了来自各种肾癌亚型的单细胞RNA测序(scRNA-seq)数据。先进的分析技术,包括统一流形近似和投影(UMAP)和反应组基因集变异分析(ReactomeGSA),用于评估细胞异质性和途径活性。使用CytoTRACE研究了巨噬细胞的发育动力学,并分析了细胞间的通信,以识别特定亚型的交互网络。
■我们的综合分析揭示了RCC内显著的细胞多样性。确定了不同的巨噬细胞和CAF亚群,每个都表现出独特的基因表达谱和途径活性。值得注意的是,ccRCC显示巨噬细胞和CAFs之间显著的双向通信,而chRCC和pRCC显示信号通路中断。代谢通路分析反映了巨噬细胞和CAFs对肿瘤微环境的适应性,MIF信号通路被确定为细胞相互作用的关键介质。
■该研究强调了RCC亚型中的蜂窝异质性和复杂的通信网络,强调了肿瘤微环境的复杂性。我们的发现表明,靶向特定的细胞相互作用和途径可能为RCC的治疗干预提供新的途径。RCC亚型的独特巨噬细胞和CAF谱为制定个性化和针对性治疗策略提供了有价值的见解。
UNASSIGNED: Renal cell carcinoma (RCC) is characterized by its heterogeneity and the complexity of its tumor microenvironment. This study addresses the need to understand RCC at a cellular level, with a focus on its three main subtypes: clear cell (ccRCC), chromophobe (chRCC), and papillary renal cell carcinoma (pRCC).
UNASSIGNED: This study aims to comprehensively characterize the cellular diversity and intercellular communication networks of RCC subtypes using scRNA-seq technology. By focusing on macrophages and cancer-associated fibroblasts (CAFs), we seek to reveal their functional states, developmental trajectories, and signaling pathways.
UNASSIGNED: We utilized single-cell RNA sequencing (scRNA-seq) data from various kidney cancer subtypes. Advanced analytical techniques, including Uniform Manifold Approximation and Projection (UMAP) and Reactome Gene Set Variation Analysis (ReactomeGSA), were employed to assess cellular heterogeneity and pathway activities. The developmental dynamics of macrophages were studied using CytoTRACE, and cell-to-cell communication was analyzed to identify subtype-specific interaction networks.
UNASSIGNED: Our comprehensive analysis revealed significant cellular diversity within RCC. Distinct macrophage and CAF subpopulations were identified, each exhibiting unique gene expression profiles and pathway activities. Notably, ccRCC showed prominent bidirectional communication between macrophages and CAFs, while chRCC and pRCC displayed disrupted signaling pathways. Metabolic pathway analysis reflected the adaptability of macrophages and CAFs to the tumor microenvironment, and the MIF signaling pathway was identified as a key mediator of cellular interactions.
UNASSIGNED: The study highlights the cellular heterogeneity and the intricate communication networks within RCC subtypes, underscoring the complexity of the tumor microenvironment. Our findings suggest that targeting specific cellular interactions and pathways may offer new avenues for therapeutic intervention in RCC. The unique macrophage and CAF profiles across RCC subtypes provide valuable insights for the development of personalized and targeted treatment strategies.