多形性胶质母细胞瘤（GBM）是最致命的脑肿瘤之一，其特点是高度异质性。虽然单细胞转录组学研究揭示了广泛的肿瘤内异质性，揭示了肿瘤内的多样性，但空间复杂性在很大程度上仍未被探索。本研究利用临床 GBM 标本，采用空间转录组学技术来深入研究基因表达异质性。我们的研究揭示了坏死边界区域和瘤周区域组织干细胞特征的显着富集，与间充质亚型特征呈正相关。此外，这些区域中上调的基因与细胞外基质（ECM）-受体相互作用、蛋白聚糖以及血管内皮生长因子（VEGF）和血管生成素-Tie（ANGPT）信号通路有关。相比之下，与糖原代谢和氧化磷酸化相关的特征与病理分区无关，而肌酸代谢特征明显是血管丰富区域所独有的。这些空间概况不仅提供了有价值的参考，还为未来深入研究 GBM 进展的功能和机制铺平了道路。© 2024 作者。

Glioblastoma multiforme (GBM) is one of the most lethal brain tumors, characterized by profound heterogeneity. While single-cell transcriptomic studies have revealed extensive intra-tumor heterogeneity, shed light on intra-tumor diversity, spatial intricacies remain largely unexplored. Leveraging clinical GBM specimens, this study employs spatial transcriptomics technology to delve into gene expression heterogeneity. Our investigation unveils a significant enrichment of tissue stem cell signature in regions bordering necrosis and the peritumoral area, positively correlated with the mesenchymal subtype signature. Moreover, upregulated genes in these regions are linked with extracellular matrix (ECM)-receptor interaction, proteoglycans, as well as vascular endothelial growth factor (VEGF) and angiopoietin-Tie (ANGPT) signaling pathways. In contrast, signatures related to glycogen metabolism and oxidative phosphorylation show no relevance to pathological zoning, whereas creatine metabolism signature is notably exclusive to vascular-enriched areas. These spatial profiles not only offer valuable references but also pave the way for future in-depth functional and mechanistic investigations into GBM progression.© 2024 The Author(s).