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Childhood cerebellar tumours mirror conserved fetal transcriptional programs

Author

Listed:
  • Maria C. Vladoiu

    (The Hospital for Sick Children
    The Hospital for Sick Children
    University of Toronto)

  • Ibrahim El-Hamamy

    (Ontario Institute for Cancer Research
    University of Toronto)

  • Laura K. Donovan

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Hamza Farooq

    (The Hospital for Sick Children
    The Hospital for Sick Children
    University of Toronto)

  • Borja L. Holgado

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Yogi Sundaravadanam

    (Ontario Institute for Cancer Research)

  • Vijay Ramaswamy

    (The Hospital for Sick Children
    The Hospital for Sick Children
    The Hospital for Sick Children)

  • Liam D. Hendrikse

    (The Hospital for Sick Children
    The Hospital for Sick Children
    University of Toronto)

  • Sachin Kumar

    (The Hospital for Sick Children
    The Hospital for Sick Children
    University of Toronto)

  • Stephen C. Mack

    (Baylor College of Medicine)

  • John J. Y. Lee

    (The Hospital for Sick Children
    The Hospital for Sick Children
    University of Toronto)

  • Vernon Fong

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Kyle Juraschka

    (The Hospital for Sick Children
    The Hospital for Sick Children
    University of Toronto)

  • David Przelicki

    (The Hospital for Sick Children
    The Hospital for Sick Children
    University of Toronto)

  • Antony Michealraj

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Patryk Skowron

    (The Hospital for Sick Children
    The Hospital for Sick Children
    University of Toronto)

  • Betty Luu

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Hiromichi Suzuki

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • A. Sorana Morrissy

    (University of Calgary)

  • Florence M. G. Cavalli

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Livia Garzia

    (Cancer Research Program, McGill University Health Centre Research Institute)

  • Craig Daniels

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Xiaochong Wu

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Maleeha A. Qazi

    (McMaster University
    McMaster University)

  • Sheila K. Singh

    (McMaster University
    McMaster University
    McMaster University)

  • Jennifer A. Chan

    (University of Calgary)

  • Marco A. Marra

    (Canada’s Michael Smith Genome Sciences Centre, BC Cancer Agency
    University of British Columbia)

  • David Malkin

    (University of Toronto)

  • Peter Dirks

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Lawrence Heisler

    (Ontario Institute for Cancer Research)

  • Trevor Pugh

    (University of Toronto
    University Health Network
    Ontario Institute for Cancer Research, 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
    Jewish General Hospital)

  • 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
    The Hospital for Sick Children
    University of Toronto
    The Hospital for Sick Children)

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.

Suggested Citation

  • 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 , 2019. "Childhood cerebellar tumours mirror conserved fetal transcriptional programs," Nature, Nature, vol. 572(7767), pages 67-73, August.
    • Handle: RePEc:nat:nature:v:572:y:2019:i:7767:d:10.1038_s41586-019-1158-7
    DOI: 10.1038/s41586-019-1158-7
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    Citations

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    Cited by:

    1. Akram A. Hamed & Daniel J. Kunz & Ibrahim El-Hamamy & Quang M. Trinh & Omar D. Subedar & Laura M. Richards & Warren Foltz & Garrett Bullivant & Matthaeus Ware & Maria C. Vladoiu & Jiao Zhang & Antony , 2022. "A brain precursor atlas reveals the acquisition of developmental-like states in adult cerebral tumours," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Petr Smirnov & Moritz J. Przybilla & Milena Simovic-Lorenz & R. Gonzalo Parra & Hana Susak & Manasi Ratnaparkhe & John KL. Wong & Verena Körber & Jan-Philipp Mallm & George Philippos & Martin Sill & T, 2024. "Multi-omic and single-cell profiling of chromothriptic medulloblastoma reveals genomic and transcriptomic consequences of genome instability," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. April A. Apfelbaum & Eric Morin & Dominik Sturm & Georges Ayoub & Jeromy DiGiacomo & Sher Bahadur & Bhavyaa Chandarana & Phoebe C. Power & Margaret M. Cusick & Dana Novikov & Prem Prabhakar & Robert E, 2025. "A diverse landscape of FGFR alterations and co-mutations suggests potential therapeutic strategies in pediatric low-grade gliomas," Nature Communications, Nature, vol. 16(1), pages 1-23, December.
    4. Rachael G. Aubin & Emma C. Troisi & Javier Montelongo & Adam N. Alghalith & Maclean P. Nasrallah & Mariarita Santi & Pablo G. Camara, 2022. "Pro-inflammatory cytokines mediate the epithelial-to-mesenchymal-like transition of pediatric posterior fossa ependymoma," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Muyang Ge & Jishuai Miao & Ji Qi & Xiaocheng Zhou & Zhixiang Lin, 2025. "TIVelo: RNA velocity estimation leveraging cluster-level trajectory inference," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    6. Sibo Zhao & Jia Li & Huiyuan Zhang & Lin Qi & Yuchen Du & Mari Kogiso & Frank K. Braun & Sophie Xiao & Yulun Huang & Jianfang Li & Wan-Yee Teo & Holly Lindsay & Patricia Baxter & Jack M. F. Su & Adeku, 2022. "Epigenetic Alterations of Repeated Relapses in Patient-matched Childhood Ependymomas," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    7. Min Kyung Lee & Nasim Azizgolshani & Ze Zhang & Laurent Perreard & Fred W. Kolling & Lananh N. Nguyen & George J. Zanazzi & Lucas A. Salas & Brock C. Christensen, 2024. "Associations in cell type-specific hydroxymethylation and transcriptional alterations of pediatric central nervous system tumors," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    8. Maxwell P. Gold & Winnie Ong & Andrew M. Masteller & David R. Ghasemi & Julie Anne Galindo & Noel R. Park & Nhan C. Huynh & Aneesh Donde & Veronika Pister & Raul A. Saurez & Maria C. Vladoiu & Grace H, 2024. "Developmental basis of SHH medulloblastoma heterogeneity," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    9. David R. Ghasemi & Konstantin Okonechnikov & Anne Rademacher & Stephan Tirier & Kendra K. Maass & Hanna Schumacher & Piyush Joshi & Maxwell P. Gold & Julia Sundheimer & Britta Statz & Ahmet S. Rifaiog, 2024. "Compartments in medulloblastoma with extensive nodularity are connected through differentiation along the granular precursor lineage," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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