加拿大多伦多大学的Michael D. Taylor研究组与多个研究组合作发现，儿童小脑瘤能够反映保守的胎儿时期转录谱。相关论文发表在2019年8月1日出版的国际学术期刊《自然》上。

研究人员利用单细胞转录组研究了来自发育中小鼠小脑的6万多个细胞，并发现幼年时期小脑瘤中不同分子亚群能够反映来自不同的、暂时性的小脑细胞谱系的转录组情况。Sonic Hedgehog髓母细胞瘤亚群于预期一样在转录上反映了granule cell特征，而group 3髓母细胞瘤类似于Nestin阳性干细胞，group 4髓母细胞瘤类似于unipolar brush cell，此外PFA/PFB室管膜瘤与小脑毛细胞型星形细胞瘤则类似于产前胶质生成前体细胞。此外，儿童小脑瘤的单细胞转录组结果表明许多大型肿瘤包含了不同分化来源的多种细胞类型。因此，这项工作表明小脑瘤是早期大脑发育过程中的疾病，并为小脑瘤为何主要发生在儿童时期提供了一个可能的解释。

据介绍，对小脑瘤起源于发展的研究受阻于小脑细胞在发育过程中变化的复杂性与异质性。

附：英文原文

Title: Childhood cerebellar tumours mirror conserved fetal transcriptional programs

Author: Maria C. Vladoiu, Ibrahim El-Hamamy, Laura K. Donovan, Hamza Farooq, Borja L. Holgado, Yogi Sundaravadanam, Vijay Ramaswamy, Liam D. Hendrikse, Sachin Kumar, Stephen C. Mack, John J. Y. Lee, Vernon Fong, Kyle Juraschka, David Przelicki, Antony Michealraj, Patryk Skowron, Betty Luu, Hiromichi Suzuki, A. Sorana Morrissy, Florence M. G. Cavalli, Livia Garzia, Craig Daniels, Xiaochong Wu, Maleeha A. Qazi, Sheila K. Singh, Jennifer A. Chan, Marco A. Marra, David Malkin, Peter Dirks, Lawrence Heisler, Trevor Pugh, Karen Ng, Faiyaz Notta, Eric M. Thompson, Claudia L. Kleinman, Alexandra L. Joyner, Nada Jabado, Lincoln Stein, Michael D. Taylor

Issue&Volume:Volume 572 Issue 7767

Abstract: Study of the origin and development of cerebellar tumours has been hampered by the complexity and heterogeneity of cerebellar cells that change over the course of development. Here we use single-cell transcriptomics to study more than 60,000 cells from the developing mouse cerebellum and show that different molecular subgroups of childhood cerebellar tumours mirror the transcription of cells from distinct, temporally restricted cerebellar lineages. The Sonic Hedgehog medulloblastoma subgroup transcriptionally mirrors the granule cell hierarchy as expected, while group 3 medulloblastoma resembles Nestin+ stem cells, group 4 medulloblastoma resembles unipolar brush cells, and PFA/PFB ependymoma and cerebellar pilocytic astrocytoma resemble the prenatal gliogenic progenitor cells. Furthermore, single-cell transcriptomics of human childhood cerebellar tumours demonstrates that many bulk tumours contain a mixed population of cells with divergent differentiation. Our data highlight cerebellar tumours as a disorder of early brain development and provide a proximate explanation for the peak incidence of cerebellar tumours in early childhood.

DOI: 10.1038/s41586-019-1158-7

Source:https://www.nature.com/articles/s41586-019-1158-7