TY  - JOUR
AU  - Ghasemi, David R
AU  - Okonechnikov, Konstantin
AU  - Rademacher, Anne
AU  - Tirier, Stephan
AU  - Maass, Kendra K
AU  - Schumacher, Hanna
AU  - Joshi, Piyush
AU  - Gold, Maxwell P
AU  - Sundheimer, Julia
AU  - Statz, Britta
AU  - Rifaioglu, Ahmet S
AU  - Bauer, Katharina
AU  - Schumacher, Sabrina
AU  - Bortolomeazzi, Michele
AU  - Giangaspero, Felice
AU  - Ernst, Kati
AU  - Clifford, Steven C
AU  - Saez-Rodriguez, Julio
AU  - Jones, David
AU  - Kawauchi, Daisuke
AU  - Fraenkel, Ernest
AU  - Mallm, Jan-Philipp
AU  - Rippe, Karsten
AU  - Korshunov, Andrey
AU  - Pfister, Stefan
AU  - Pajtler, Kristian
TI  - Compartments in medulloblastoma with extensive nodularity are connected through differentiation along the granular precursor lineage.
JO  - Nature Communications
VL  - 15
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2024-00070
SP  - 269
PY  - 2024
N1  - #EA:B062#LA:B300#LA:B062#
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:38191550
DO  - DOI:10.1038/s41467-023-44117-x
UR  - https://inrepo02.dkfz.de/record/286731
ER  -