由美国麻省总医院、哈佛医学院、布罗德研究所和圣犹大儿童研究医院的专家联合牵头的国际科研团队取得一项新突破，他们提出了用单细胞基因组学的方法分析了成神经管细胞瘤的细胞结构。相关论文发表在2019年8月1日出版的《自然》上。

研究团队利用单细胞转录组学研究了囊括成神经管细胞瘤所有四种分子亚型的25种成神经管细胞瘤样本中的肿瘤内和肿瘤间的异质性。他们发现WNT亚型，SHH亚型和组3亚型包括了亚型特异性的未分化神经元样恶性肿瘤细胞群体和分化神经元样特性肿瘤细胞群体。但是，组4亚型仅仅由分化的神经元样肿瘤细胞组成。SHH亚型跟处于和患者年龄相关的不同分化状态的颗粒神经元非常相似。组3和组4亚型则显示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，并且能够通过这两种细胞亚型的相对比例区分彼此。跨物种转录组学分析则将不同谷氨酸种群体定义为SHH亚型和组4亚型的假定来推测细胞来源。总之，这些实验数据对亚型特异性的成神经管瘤细胞生物学和发育生物学研究提供了新的见解。

研究人员表示，成神经管细胞瘤是一种恶性儿童小脑肿瘤类型，包含了不同的分子亚型。尽管这些亚型的基因组特性已经得到明确定义，但是细胞多样性在多大程度上决定了它们不同的生物学和临床行为？仍然有待探索。

附：英文原文

Title: Resolving medulloblastoma cellular architecture by single-cell genomics

Author: Volker Hovestadt

Issue&Volume: Volume 572 Issue 7767

Abstract: 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.

DOI: 10.1038/s41586-019-1434-6

Source:https://www.nature.com/articles/s41586-019-1434-6