Ependymoma is a heterogeneous entity of central nervous system tumors with well-established molecular groups. Here, we apply single-cell RNA sequencing to analyze ependymomas across molecular groups and anatomic locations to investigate their intratumoral heterogeneity and developmental origins. Ependymomas are composed of a cellular hierarchy initiating from undifferentiated populations, which undergo impaired differentiation toward three lineages of neuronal-glial fate specification. While prognostically favorable groups of ependymoma predominantly harbor differentiated cells, aggressive groups are enriched for undifferentiated cell populations. The delineated transcriptomic signatures correlate with patient survival and define molecular dependencies for targeted treatment approaches. Taken together, our analyses reveal a developmental hierarchy underlying ependymomas relevant to biological and clinical behavior.

室管膜瘤是中枢神经系统肿瘤的异质实体，具有完善的分子群。在这里，我们应用单细胞 RNA 测序来分析不同分子组和解剖位置的室管膜瘤，以研究其瘤内异质性和发育起源。室管膜瘤由未分化群体起始的细胞层次结构组成，这些群体经历了向神经元-胶质细胞命运规范的三个谱系的分化受损。虽然预后良好的室管膜瘤组主要含有分化细胞​​，但侵袭性组则富含未分化细胞群。所描绘的转录组特征与患者的生存相关，并定义了靶向治疗方法的分子依赖性。综合起来，