Childhood cerebellar tumours mirror conserved fetal transcriptional programs

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 () and Michael D. Taylor ()
Additional contact information
Maria C. Vladoiu: The Hospital for Sick Children
Ibrahim El-Hamamy: Ontario Institute for Cancer Research
Laura K. Donovan: The Hospital for Sick Children
Hamza Farooq: The Hospital for Sick Children
Borja L. Holgado: The Hospital for Sick Children
Yogi Sundaravadanam: Ontario Institute for Cancer Research
Vijay Ramaswamy: The Hospital for Sick Children
Liam D. Hendrikse: The Hospital for Sick Children
Sachin Kumar: The Hospital for Sick Children
Stephen C. Mack: Baylor College of Medicine
John J. Y. Lee: The Hospital for Sick Children
Vernon Fong: The Hospital for Sick Children
Kyle Juraschka: The Hospital for Sick Children
David Przelicki: The Hospital for Sick Children
Antony Michealraj: The Hospital for Sick Children
Patryk Skowron: The Hospital for Sick Children
Betty Luu: The Hospital for Sick Children
Hiromichi Suzuki: The Hospital for Sick Children
A. Sorana Morrissy: University of Calgary
Florence M. G. Cavalli: The Hospital for Sick Children
Livia Garzia: Cancer Research Program, McGill University Health Centre Research Institute
Craig Daniels: The Hospital for Sick Children
Xiaochong Wu: The Hospital for Sick Children
Maleeha A. Qazi: McMaster University
Sheila K. Singh: McMaster University
Jennifer A. Chan: University of Calgary
Marco A. Marra: Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency
David Malkin: University of Toronto
Peter Dirks: The Hospital for Sick Children
Lawrence Heisler: Ontario Institute for Cancer Research
Trevor Pugh: University of Toronto
Karen Ng: Ontario Institute for Cancer Research, Toronto
Faiyaz Notta: Ontario Institute for Cancer Research, Toronto
Eric M. Thompson: Duke University Medical Center
Claudia L. Kleinman: McGill University
Alexandra L. Joyner: Memorial Sloan-Kettering Cancer Center
Nada Jabado: McGill University
Lincoln Stein: Ontario Institute for Cancer Research
Michael D. Taylor: The Hospital for Sick Children

Nature, 2019, vol. 572, issue 7767, 67-73

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41586-019-1158-7

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