Resolving medulloblastoma cellular architecture by single-cell genomics
Resolving medulloblastoma cellular architecture by single-cell genomics
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DOI：
10.1038/s41586-019-1434-6
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发表时间：
2019-08-01
期刊：
影响因子：
64.8
通讯作者：
Northcott, Paul A.
中科院分区：
文献类型：
--
作者：
Hovestadt, Volker;Smith, Kyle S.;Northcott, Paul A.
髓母细胞瘤是一种儿童小脑恶性肿瘤类型，包括不同的分子亚群。虽然这些亚群的基因组特征是明确的，但细胞多样性在多大程度上构成了它们不同的生物学和临床行为的基础，这在很大程度上尚未探索。在这里，我们使用单细胞转录组学研究肿瘤内和肿瘤间的异质性在25髓母细胞瘤跨越所有分子亚组。WNT、SHH和第3组肿瘤包括亚组特异性未分化和分化的神经元样恶性细胞群，而第4组肿瘤仅由分化的神经元样肿瘤细胞组成。SHH肿瘤非常类似于与患者年龄相关的不同分化状态的颗粒神经元。第3组和第4组肿瘤表现出从原始祖细胞样细胞到更成熟的神经元样细胞的发育轨迹，其相对比例区分了这些亚组。跨物种转录组学定义不同的amatergic人群作为假定的细胞的起源SHH和组4亚型。总的来说，这些数据提供了深入了解亚型特异性髓母细胞瘤生物学的细胞和发育状态。
Medulloblastoma is a malignant childhood cerebellar tumour type that comprises distinct molecular subgroups. Whereas genomic characteristics of these subgroups are well defined, the extent to which cellular diversity underlies their divergent biology and clinical behaviour remains largely unexplored. Here we used single-cell transcriptomics to investigate intra- and intertumoral heterogeneity in 25 medulloblastomas spanning all molecular subgroups. WNT, SHH and Group 3 tumours comprised subgroup-specific undifferentiated and differentiated neuronal-like malignant populations, whereas Group 4 tumours consisted exclusively of differentiated neuronal-like neoplastic cells. SHH tumours closely resembled granule neurons of varying differentiation states that correlated with patient age. Group 3 and Group 4 tumours exhibited a developmental trajectory from primitive progenitor-like to more mature neuronal-like cells, the relative proportions of which distinguished these subgroups. Cross-species transcriptomics defined distinct glutamatergic populations as putative cells-of-origin for SHH and Group 4 subtypes. Collectively, these data provide insights into the cellular and developmental states underlying subtype-specific medulloblastoma biology.