研究动态
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单细胞RNA测序显示,高AQP4表达的恶性胶质瘤中,胶质瘤相关巨噬细胞极化和细胞状态发生了变化。

Single-cell RNA sequencing reveals changes in glioma-associated macrophage polarization and cellular states of malignant gliomas with high AQP4 expression.

发表日期:2023 Jan 04
作者: Ran Wang, Lu Peng, Yong Xiao, Qi Zhou, Zhen Wang, Lei Tang, Hong Xiao, Kun Yang, Hongyi Liu, Li Li
来源: CANCER GENE THERAPY

摘要:

胶质母细胞瘤是成年人最常见的原发性中枢神经系统肿瘤。脑中的AQP4编码的水通道蛋白作为一种水通道蛋白,据报道会改变聚集状态以影响细胞质膜动力学,提供肿瘤细胞及肿瘤微环境成分转移的潜力。我们对13个恶性胶质母细胞瘤样本中的53059个细胞进行单细胞RNA转录组测序,并发现AQP4的表达在不同样本中是不同的。在TCGA的胶质母细胞瘤数据库中也观察到了相同的结果,显示AQP4高表达群体的总生存率和对化疗的反应都较差。与AQP4高表达相伴随的是,与免疫系统相关的基因也过度表达,如CD74、HES1、CALD1和HEBP2,表明AQP4可能与肿瘤进展的免疫因素有关。我们还发现,肿瘤相关巨噬细胞在高AQP4组中趋于极化为M2巨噬细胞。在胶质母细胞瘤样本中,我们检查了细胞状态的差异,并确定了细胞状态根据AQP4表达水平的不同而异。简而言之,我们的研究揭示了不同AQP4表达水平的恶性胶质母细胞瘤中存在很大的异质性,表明肿瘤细胞和肿瘤免疫环境之间存在错综复杂的联系。 ©2022作者。
Glioma is the most common primary central nervous system tumor in adults. Aquaporin-4, as a water channel protein encoded by AQP4 in the brain, is reported to alter its aggregation status to affect plasma membrane dynamics and provide the potential for metastasis of tumor cells and components of the tumor microenvironment. We performed single-cell RNA transcriptome sequencing of 53059 cells from 13 malignant glioma samples and spotted that the expression of AQP4 differed between samples. The same result was observed in the TCGA glioma database, showing poor overall survival and poor response to chemotherapy in AQP4 overexpressed populations. Concomitant with the overexpression of AQP4, genes related to the immune system were also over-expressed, such as CD74, HES1, CALD1, and HEBP2, indicating AQP4 may relate to immune factors of tumor progression. We also found that tumor-associated macrophages tended to polarize toward M2 macrophages in the high AQP4 group. In glioblastoma samples, we examined cell status differences and identified that cell status differs according to AQP4 expression levels. Briefly, our study revealed substantial heterogeneity within malignant gliomas with different AQP4 expression levels, indicating the intricate connection between tumor cells and the tumor immune environment.© 2022. The Author(s).