Compartments in medulloblastoma with extensive nodularity are connected through differentiation along the granular precursor lineage
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Published:2024-01-08
Issue:1
Volume:15
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Ghasemi David R.ORCID, Okonechnikov Konstantin, Rademacher AnneORCID, Tirier Stephan, Maass Kendra K., Schumacher HannaORCID, Joshi Piyush, Gold Maxwell P.ORCID, Sundheimer JuliaORCID, Statz Britta, Rifaioglu Ahmet S., Bauer Katharina, Schumacher Sabrina, Bortolomeazzi Michele, Giangaspero FeliceORCID, Ernst Kati J.ORCID, Clifford Steven C.ORCID, Saez-Rodriguez JulioORCID, Jones David T. W.ORCID, Kawauchi DaisukeORCID, Fraenkel Ernest, Mallm Jan-PhilippORCID, Rippe KarstenORCID, Korshunov Andrey, Pfister Stefan M.ORCID, Pajtler Kristian W.ORCID
Abstract
AbstractMedulloblastomas 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.
Funder
Ein Kiwi gegen Krebs Foundation Studienstiftung des Deutschen Volkes Deutsche Krebshilfe Ministry of Science, Research and the Arts Baden-Württemberg German Federal Ministry of Education and Research, grant: CompLS DeepSC2
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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