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

Compartments in medulloblastoma with extensive nodularity are connected through differentiation along the granular precursor lineage.
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DOI:
10.1038/s41467-023-44117-x
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发表时间:
2024-01-08
影响因子:
16.6
通讯作者:
Pajtler, Kristian W.
Pajtler, Kristian W.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Ghasemi, David R.;Okonechnikov, Konstantin;Rademacher, Anne;Tirier, Stephan;Maass, Kendra K.;Schumacher, Hanna;Joshi, Piyush;Gold, Maxwell P.;Sundheimer, Julia;Statz, Britta;Rifaioglu, Ahmet S.;Bauer, Katharina;Schumacher, Sabrina;Bortolomeazzi, Michele;Giangaspero, Felice;Ernst, Kati J.;Clifford, Steven C.;Saez-Rodriguez, Julio;Jones, David T. W.;Kawauchi, Daisuke;Fraenkel, Ernest;Mallm, Jan-Philipp;Rippe, Karsten;Korshunov, Andrey;Pfister, Stefan M.;Pajtler, Kristian W.

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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. The mechanisms regulating the balance between proliferation and differentiation in medulloblastomas with extensive nodularity (MBEN) remain poorly understood. Here, single cell multi-omics and spatial analysis characterises the spatial tissue organisation of MBEN in the context of the developmental trajectory.
结节过度的髓母细胞瘤:放射学特征和病理相关性。
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