背景:间变性室管膜瘤和H3K27M突变型弥漫性中线胶质瘤是两种常见的脑肿瘤亚型,长期预后较差。本研究通过单细胞RNA测序(scRNA-seq)技术分析和比较了两种肿瘤之间细胞类型的差异。
方法:对来自间变性室管膜瘤患者和H3K27M突变的弥漫性中线神经胶质瘤患者的癌组织进行ScRNA-seq分析。细胞聚集,标记基因鉴定,单元格类型批注,然后对差异表达基因进行拷贝数变异分析和功能分析。
结果:从间变性室管膜瘤和H3K27M突变型弥漫性中线神经胶质瘤中获得总共11,219个细胞,这些细胞分为12个不同的簇。每个细胞簇可以用特定的细胞标记物表征以指示细胞异质性。在每个样品中注释了五种细胞类型,包括星形胶质细胞,少突胶质细胞,小胶质细胞,神经祖细胞和免疫细胞。两种脑肿瘤之间的簇类型和细胞类型的比例不一致。功能分析表明,这些细胞簇参与肿瘤相关途径,两种肿瘤的起源细胞略有不同。此外,细胞通讯分析表明,NRG3-ERBB4对是间变性室管膜瘤的关键配体-受体对,而在H3K27M突变型弥漫性中线神经胶质瘤中,PTN-PTPRZ1对建立与其他细胞的接触.
结论:间变性室管膜瘤和H3K27M突变型弥漫性中线胶质瘤存在瘤内异质性,亚型差异可能是由于细胞起源的差异。
BACKGROUND: Anaplastic ependymoma and H3K27M-mutant diffuse midline glioma are two common subtypes of brain tumors with poor long-term prognosis. The present study analyzed and compared the differences in cell types between two tumors by single-cell RNA sequencing (scRNA-seq) technology.
METHODS: ScRNA-seq was performed to profile cells from cancer tissue from anaplastic ependymoma patient and H3K27M-mutant diffuse midline glioma patient. Cell clustering, marker gene identification, cell type annotation, copy number variation analysis and function analysis of differentially expressed genes were then performed.
RESULTS: A total of 11,219 cells were obtained from anaplastic ependymoma and H3K27M mutant diffuse midline glioma, and these cells categorized into 12 distinct clusters. Each cell cluster could be characterized with specific cell markers to indicate cellular heterogeneity. Five cell types were annotated in each sample, including astrocyte, oligodendrocytes, microglial cell, neural progenitor cell and immune cell. The cluster types and proportion of cell types were not consistent between the two brain tumors. Functional analyses suggest that these cell clusters are involved in tumor-associated pathways, with slight differences in the cells of origin between the two tumors. In addition, cell communication analysis showed that the NRG3-ERBB4 pair is a key Ligand-receptor pair for anaplastic ependymoma, while in H3K27M-mutant diffuse midline glioma it is the PTN-PTPRZ1 pair that establishes contact with other cells.
CONCLUSIONS: There was intratumor heterogeneity in anaplastic ependymoma and H3K27M mutant diffuse midline glioma, and that the subtype differences may be due to differences in the origin of the cells.