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Childhood cerebellar tumours mirror conserved fetal transcriptional programs.

Nature | 2019

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.

Pubmed ID: 31043743 RIS Download

Research resources used in this publication

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Antibodies used in this publication

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Associated grants

  • Agency: NIMH NIH HHS, United States
    Id: R37 MH085726
  • Agency: NCI NIH HHS, United States
    Id: P30 CA008748
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS092096
  • Agency: NCI NIH HHS, United States
    Id: R01 CA148699
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS106155
  • Agency: NCI NIH HHS, United States
    Id: R01 CA159859
  • Agency: NCI NIH HHS, United States
    Id: R01 CA192176

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Allen Developing Mouse Brain Atlas (tool)

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Map of gene expression in developing mouse brain revealing gene expression patterns from embryonic through postnatal stages. Provides information about spatial and temporal regulation of gene expression with database. Feature include seven sagittal reference atlases created with a developmental ontology. These anatomic atlases may be viewed alongside in situ hybridization (ISH) data as well as by itself.

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RRID:SCR_005622

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RRID:SCR_006406

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RRID:SCR_016341

Software as R package designed for QC, analysis, and exploration of single cell RNA-seq data. Enable users to identify and interpret sources of heterogeneity from single cell transcriptomic measurements, and to integrate diverse types of single cell data.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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