Glioblastoma is characterized by heterogeneous malignant cells that are functionally integrated within the neuroglial microenvironment. Here, we model this ecosystem by growing glioblastoma into long-term cultured human cortical organoids that contain the major neuroglial cell types found in the cerebral cortex. Single-cell RNA-seq analysis suggests that, compared to matched gliomasphere models, glioblastoma cortical organoids (GCO) more faithfully recapitulate the diversity and expression programs of malignant cell states found in patient tumors. Additionally, we observe widespread transfer of glioblastoma transcripts and GFP proteins to non-malignant cells in the organoids. Mechanistically, this transfer involves extracellular vesicles and is biased towards defined glioblastoma cell states and astroglia cell types. These results extend previous glioblastoma-organoid modeling efforts and suggest widespread intercellular transfer in the glioblastoma neuroglial microenvironment.

中文翻译：

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胶质母细胞瘤-皮质类器官概括了细胞状态异质性和细胞间转移


胶质母细胞瘤的特征是异质性恶性细胞，这些细胞在功能上整合到神经胶质细胞微环境中。在这里，我们通过将胶质母细胞瘤培养成长期培养的人类皮质类器官来模拟这个生态系统，这些类器官包含大脑皮层中发现的主要神经胶质细胞类型。单细胞 RNA-seq 分析表明，与匹配的胶质瘤球模型相比，胶质母细胞瘤皮质类器官 （GCO） 更忠实地概括了患者肿瘤中发现的恶性细胞状态的多样性和表达程序。此外，我们观察到胶质母细胞瘤转录物和 GFP 蛋白广泛转移到类器官中的非恶性细胞。从机制上讲，这种转移涉及细胞外囊泡，并且偏向于确定的胶质母细胞瘤细胞状态和星形胶质细胞类型。这些结果扩展了以前的胶质母细胞瘤-类器官建模工作，并表明胶质母细胞瘤神经胶质细胞微环境中的广泛细胞间转移。