Childhood brain tumors have suspected prenatal origins. To identify vulnerable developmental states, we generated a single-cell transcriptome atlas of >65,000 cells from embryonal pons and forebrain, two major tumor locations. We derived signatures for 191 distinct cell populations and defined the regional cellular diversity and differentiation dynamics. Projection of bulk tumor transcriptomes onto this dataset shows that WNT medulloblastomas match the rhombic lip-derived mossy fiber neuronal lineage and embryonal tumors with multilayered rosettes fully recapitulate a neuronal lineage, while group 2a/b atypical teratoid/rhabdoid tumors may originate outside the neuroectoderm. Importantly, single-cell tumor profiles reveal highly defined cell hierarchies that mirror transcriptional programs of the corresponding normal lineages. Our findings identify impaired differentiation of specific neural progenitors as a common mechanism underlying these pediatric cancers and provide a rational framework for future modeling and therapeutic interventions.

中文翻译：

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停滞的发展计划是小儿脑肿瘤的根源。

儿童脑瘤疑似产前起源。为了识别易受伤害的发育状态，我们从胚胎脑桥和前脑这两个主要肿瘤位置生成了超过 65,000 个细胞的单细胞转录组图谱。我们获得了 191 个不同细胞群的特征，并定义了区域细胞多样性和分化动力学。大量肿瘤转录组在该数据集上的投影表明，WNT 髓母细胞瘤与菱形唇源性苔藓纤维神经元谱系相匹配，具有多层玫瑰花结的胚胎肿瘤完全概括了神经元谱系，而 2a/b 组非典型畸胎瘤样/横纹肌样瘤可能起源于神经外胚层之外。重要的是，单细胞肿瘤概况揭示了高度定义的细胞层次结构，这些层次结构反映了相应正常谱系的转录程序。