1. Childhood cerebellar tumours mirror conserved fetal transcriptional programs.
- Author
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Vladoiu MC, El-Hamamy I, Donovan LK, Farooq H, Holgado BL, Sundaravadanam Y, Ramaswamy V, Hendrikse LD, Kumar S, Mack SC, Lee JJY, Fong V, Juraschka K, Przelicki D, Michealraj A, Skowron P, Luu B, Suzuki H, Morrissy AS, Cavalli FMG, Garzia L, Daniels C, Wu X, Qazi MA, Singh SK, Chan JA, Marra MA, Malkin D, Dirks P, Heisler L, Pugh T, Ng K, Notta F, Thompson EM, Kleinman CL, Joyner AL, Jabado N, Stein L, and Taylor MD
- Subjects
- Animals, Cerebellar Neoplasms classification, Cerebellum cytology, Cerebellum embryology, Cerebellum metabolism, Child, Female, Fetus cytology, Glioma classification, Glioma genetics, Glioma pathology, Humans, Medulloblastoma classification, Medulloblastoma genetics, Medulloblastoma pathology, Mice, Sequence Analysis, RNA, Single-Cell Analysis, Time Factors, Transcriptome genetics, Cerebellar Neoplasms genetics, Cerebellar Neoplasms pathology, Evolution, Molecular, Fetus metabolism, Gene Expression Regulation, Developmental, Gene Expression Regulation, Neoplastic, Transcription, Genetic
- 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.- Published
- 2019
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