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Compartments in medulloblastoma with extensive nodularity are connected through differentiation along the granular precursor lineage

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  • David R. Ghasemi

    (Hopp-Children’s Cancer Center Heidelberg (KiTZ)
    German Cancer Research Center (DKFZ)
    Heidelberg University Hospital)

  • Konstantin Okonechnikov

    (Hopp-Children’s Cancer Center Heidelberg (KiTZ)
    German Cancer Research Center (DKFZ))

  • Anne Rademacher

    (German Cancer Research Center (DKFZ) and Bioquant)

  • Stephan Tirier

    (German Cancer Research Center (DKFZ) and Bioquant
    Resolve BioSciences GmbH)

  • Kendra K. Maass

    (Hopp-Children’s Cancer Center Heidelberg (KiTZ)
    German Cancer Research Center (DKFZ)
    Heidelberg University Hospital)

  • Hanna Schumacher

    (Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant)

  • Piyush Joshi

    (Hopp-Children’s Cancer Center Heidelberg (KiTZ)
    German Cancer Research Center (DKFZ))

  • Maxwell P. Gold

    (Massachusetts Institute of Technology (MIT))

  • Julia Sundheimer

    (Hopp-Children’s Cancer Center Heidelberg (KiTZ)
    German Cancer Research Center (DKFZ)
    Heidelberg University)

  • Britta Statz

    (Hopp-Children’s Cancer Center Heidelberg (KiTZ)
    German Cancer Research Center (DKFZ))

  • Ahmet S. Rifaioglu

    (Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant
    İskenderun Technical University)

  • Katharina Bauer

    (German Cancer Research Center (DKFZ))

  • Sabrina Schumacher

    (German Cancer Research Center (DKFZ) and Bioquant)

  • Michele Bortolomeazzi

    (German Cancer Research Center (DKFZ))

  • Felice Giangaspero

    (Sapienza University of Rome
    Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed)

  • Kati J. Ernst

    (Hopp-Children’s Cancer Center Heidelberg (KiTZ)
    German Cancer Research Center (DKFZ))

  • Steven C. Clifford

    (Newcastle University Centre for Cancer)

  • Julio Saez-Rodriguez

    (Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant)

  • David T. W. Jones

    (Hopp-Children’s Cancer Center Heidelberg (KiTZ)
    German Cancer Research Center (DKFZ))

  • Daisuke Kawauchi

    (National Center of Neurology and Psychiatry (NCNP))

  • Ernest Fraenkel

    (Massachusetts Institute of Technology (MIT)
    Edythe Broad Institute of MIT and Harvard)

  • Jan-Philipp Mallm

    (German Cancer Research Center (DKFZ))

  • Karsten Rippe

    (German Cancer Research Center (DKFZ) and Bioquant)

  • Andrey Korshunov

    (Hopp-Children’s Cancer Center Heidelberg (KiTZ)
    Heidelberg University Hospital
    German Consortium for Translational Cancer Research (DKTK))

  • Stefan M. Pfister

    (Hopp-Children’s Cancer Center Heidelberg (KiTZ)
    German Cancer Research Center (DKFZ)
    Heidelberg University Hospital)

  • Kristian W. Pajtler

    (Hopp-Children’s Cancer Center Heidelberg (KiTZ)
    German Cancer Research Center (DKFZ)
    Heidelberg University Hospital)

Abstract

Medulloblastomas with extensive nodularity are cerebellar tumors characterized by two distinct compartments and variable disease progression. The mechanisms governing the balance between proliferation and differentiation in MBEN remain poorly understood. Here, we employ a multi-modal single cell transcriptome analysis to dissect this process. In the internodular compartment, we identify proliferating cerebellar granular neuronal precursor-like malignant cells, along with stromal, vascular, and immune cells. In contrast, the nodular compartment comprises postmitotic, neuronally differentiated malignant cells. Both compartments are connected through an intermediate cell stage resembling actively migrating CGNPs. Notably, we also discover astrocytic-like malignant cells, found in proximity to migrating and differentiated cells at the transition zone between the two compartments. Our study sheds light on the spatial tissue organization and its link to the developmental trajectory, resulting in a more benign tumor phenotype. This integrative approach holds promise to explore intercompartmental interactions in other cancers with varying histology.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44117-x
    DOI: 10.1038/s41467-023-44117-x
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