Journal
NATURE
Volume 572, Issue 7767, Pages 67-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41586-019-1158-7
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Categories
Funding
- NIH [R01CA148699, R01CA159859]
- Pediatric Brain Tumor Foundation
- Terry Fox Research Institute
- Canadian Institutes of Health Research
- Cure Search Foundation
- b.r.a.i.n. child
- Meagan's Walk
- SWIFTY Foundation
- Genome Canada
- Genome BC
- Genome Quebec
- Ontario Research Fund
- Worldwide Cancer Research
- V-Foundation for Cancer Research
- Ontario Institute for Cancer Research by the Government of Ontario
- Canadian Cancer Society Research Institute Impact grant
- Stand Up To Cancer (SU2C) St. Baldrick's Pediatric Dream Team Translational Research Grant by the Government of Canada through Genome Canada [SU2C-AACR-DT1113]
- SU2C Canada Cancer Stem Cell Dream Team Research Funding by the Government of Canada through Genome Canada [SU2C-AACR-DT-19-15]
- Garron Family Chair in Childhood Cancer Research at the Hospital for Sick Children
- University of Toronto
- Government of Ontario
- Canadian Institutes of Health Research Doctoral scholarship
- National Cancer Institute Cancer Center Support Grant [P30 CA008748-48]
- Ontario Institute for Cancer Research's Genomics & Bioinformatics platform through the Government of Ontario
- [NIMH-R37MH085726]
- [NCI-CA192176]
- [NINDS-R01NS092096]
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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.
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