Format

Send to

Choose Destination
Nature. 2019 May 1. doi: 10.1038/s41586-019-1158-7. [Epub ahead of print]

Childhood cerebellar tumours mirror conserved fetal transcriptional programs.

Author information

1
Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
2
The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
3
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
4
Computational Biology Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
5
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
6
Division of Haematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
7
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
8
Brain Tumor Program, Children's Cancer Center and Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
9
Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
10
Cancer Research Program, McGill University Health Centre Research Institute, Montreal, Quebec, Canada.
11
Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Ontario, Canada.
12
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
13
Department of Surgery, McMaster University, Hamilton, Ontario, Canada.
14
Charbonneau Cancer Institute, University of Calgary, Calgary, Alberta, Canada.
15
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada.
16
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
17
Division of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario, Canada.
18
Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
19
Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
20
Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.
21
Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
22
Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, Canada.
23
Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
24
Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada. nada.jabado@mcgill.ca.
25
Computational Biology Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada. lincoln.stein@oicr.on.ca.
26
Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada. mdt.cns@gmail.com.
27
The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada. mdt.cns@gmail.com.
28
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. mdt.cns@gmail.com.
29
Division of Neurosurgery, The Hospital for Sick Children, Toronto, Ontario, Canada. mdt.cns@gmail.com.
30
Department of Surgery and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. mdt.cns@gmail.com.

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.

PMID:
31043743
DOI:
10.1038/s41586-019-1158-7

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center