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Lookup NU author(s): Professor Steven CliffordORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024, The Author(s).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.
Author(s): Ghasemi DR, Okonechnikov K, Rademacher A, Tirier S, Maass KK, Schumacher H, Joshi P, Gold MP, Sundheimer J, Statz B, Rifaioglu AS, Bauer K, Schumacher S, Bortolomeazzi M, Giangaspero F, Ernst KJ, Clifford SC, Saez-Rodriguez J, Jones DTW, Kawauchi D, Fraenkel E, Mallm J-P, Rippe K, Korshunov A, Pfister SM, Pajtler KW
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2024
Volume: 15
Issue: 1
Online publication date: 08/01/2024
Acceptance date: 30/11/2023
Date deposited: 23/10/2024
ISSN (electronic): 2041-1723
Publisher: Nature Research
URL: https://doi.org/10.1038/s41467-023-44117-x
DOI: 10.1038/s41467-023-44117-x
Data Access Statement: The snRNA-seq and bulk-sequencing (RNA, microdissected) data have been deposited in GEO database and is available under the combined accession number GSE239854. All raw images and processed data after cell segmentation from spatial transcriptomics experiments have been deposited at the BioImage Archive and can be accessed under the accession numbers S-BIAD825, S-BIAD826. In addition, the raw counts for Molecular Cartography have been uploaded to GEO (accession number: GSE247736). The DNA methylation data copy number profiles and DNA sequencing mutation results were integrated from the corresponding medulloblastoma molecular landscape study deposited at European Genome-Phenome Archive under accession number EGAS0000100195312. All raw data acquired by DNA methylation profiling is available via GEO (accession number: GSE247741). The fastq files from DNA sequencing are available via SRA (SRA-ID: 473652, BioProject: PRJNA1044021). More at https://www.nature.com/articles/s41467-023-44117-x#d
PubMed id: 38191550
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