Wu Haoda, Fu Ruiqing, Zhang Yu-Hong, Liu Zhiming, Chen Zhen-Hua, Xu Jingkai, Tian Yongji, Jin Wenfei, Wong Samuel Zheng Hao, Wu Qing-Feng
State Key Laboratory of Molecular Development Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
Front Immunol. 2022 Jun 30;13:903246. doi: 10.3389/fimmu.2022.903246. eCollection 2022.
Ependymoma (EPN) is a malignant glial tumor occurring throughout central nervous system, which commonly presents in children. Although recent studies have characterized EPN samples at both the bulk and single-cell level, intratumoral heterogeneity across subclones remains a confounding factor that impedes understanding of EPN biology. In this study, we generated a high-resolution single-cell dataset of pediatric ependymoma with a particular focus on the comparison of subclone differences within tumors and showed upregulation of cilium-associated genes in more highly differentiated subclone populations. As a proxy to traditional pseudotime analysis, we applied a novel trajectory scoring method to reveal cellular compositions associated with poor survival outcomes across primary and relapsed patients. Furthermore, we identified putative cell-cell communication features between relapsed and primary samples and showed upregulation of pathways associated with immune cell crosstalk. Our results revealed both inter- and intratumoral heterogeneity in EPN and provided a framework for studying transcriptomic signatures of individual subclones at single-cell resolution.
室管膜瘤（EPN）是一种发生于中枢神经系统的恶性胶质瘤，常见于儿童。尽管最近的研究已在整体和单细胞水平对EPN样本进行了特征描述，但不同亚克隆之间的肿瘤内异质性仍然是一个混杂因素，阻碍了对EPN生物学的理解。在本研究中，我们生成了一个儿科室管膜瘤的高分辨率单细胞数据集，特别关注肿瘤内亚克隆差异的比较，并显示在分化程度更高的亚克隆群体中纤毛相关基因上调。作为传统伪时间分析的替代方法，我们应用了一种新的轨迹评分方法来揭示与初发和复发患者不良生存结果相关的细胞组成。此外，我们确定了复发样本和初发样本之间假定的细胞间通讯特征，并显示与免疫细胞串扰相关的信号通路上调。我们的结果揭示了EPN的肿瘤间和肿瘤内异质性，并提供了一个在单细胞分辨率下研究单个亚克隆转录组特征的框架。
