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Abstract：
Rationale: The heterogeneity of tumor cells within the glioblastoma (GBM) microenvironment presents a complex challenge in curbing GBM progression. Understanding the specific mechanisms of interaction between different GBM cell subclusters and non-tumor cells is crucial. Methods: In this study, we utilized a comprehensive approach integrating glioma single-cell and spatial transcriptomics. This allowed us to examine the molecular interactions and spatial localization within GBM, focusing on a specific tumor cell subcluster, GBM subcluster 6, and M2-type tumor-associated macrophages (M2 TAMs). Results: Our analysis revealed a significant correlation between a specific tumor cell subcluster, GBM cluster 6, and M2-type TAMs. Further in vitro and in vivo experiments demonstrated the specific regulatory role of the CEBPB transcriptional network in GBM subcluster 6, which governs its tumorigenicity, recruitment of M2 TAMs, and polarization. This regulation involves molecules such as MCP1 for macrophage recruitment and the SPP1-Integrin αvβ1-Akt signaling pathway for M2 polarization. Conclusion: Our findings not only deepen our understanding of the formation of M2 TAMs, particularly highlighting the differential roles played by heterogeneous cells within GBM in this process, but also provided new insights for effectively controlling the malignant progression of GBM.
摘要：
原理：胶质母细胞瘤（GBM）微环境中肿瘤细胞的异质性对抑制GBM进展提出了复杂的挑战。了解不同GBM细胞亚簇与非肿瘤细胞之间相互作用的具体机制至关重要。方法:在本研究中,我们使用了一种综合方法，整合了神经胶质瘤单细胞和空间转录组学。这使我们能够检查GBM内的分子相互作用和空间定位，专注于特定的肿瘤细胞亚群，GBM亚簇6和M2型肿瘤相关巨噬细胞(M2TAMs)。结果：我们的分析揭示了特定肿瘤细胞亚群之间的显着相关性，GBM簇6和M2型TAM。进一步的体外和体内实验证明了GBM亚簇6中CEBPB转录网络的特定调节作用，M2TAM的招募，和两极分化。这种调节涉及用于巨噬细胞募集的分子如MCP1和用于M2极化的SPP1-整合素αvβ1-Akt信号传导途径。结论：我们的发现不仅加深了我们对M2TAM形成的理解，特别强调了GBM内异质细胞在这一过程中所起的不同作用，同时也为有效控制GBM的恶性进展提供了新的见解。
