A coregulatory influence map of glioblastoma heterogeneity and plasticity

npj Precision Oncology, Год журнала: 2025, Номер 9(1)

Опубликована: Апрель 15, 2025

Язык: Английский

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A coregulatory influence map of glioblastoma heterogeneity and plasticity - From cells in vitro to tumors and back again

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 23, 2024

We present GBM-cRegMap, an online resource providing a comprehensive coregulatory influence network perspective on glioblastoma (GBM) heterogeneity and plasticity. Using representation learning algorithms, we derived two components of this resource: GBM-CoRegNet, highly specific tumor cells, GBM-CoRegMap, unified map based 1612 tumors from 16 studies. As widely applicable closed-loop system connecting cellular models tumors, GBM-cRegMap will provide the GBM research community with easy-to-use web tool (https://gbm.cregmap.com) that maps any existing or newly generated transcriptomic "query" data to reference large-scale manifold disease heterogeneity. demonstrated synergy between by refining molecular classification GBM, identifying potential key regulators, aligning transcriptional profiles in vitro models. Through amalgamation vast dataset, validated proneural (PN)-mesenchymal (MES) axis identified three subclasses classical (CL) tumors: astrocyte-like (CL-A), epithelial basal-like (CL-B), cilium-rich (CL-C). revealed CL-C subclass, intermediate state demonstrating plasticity cells along PN-MES under chemotherapy. such as PAX8, NKX2.5, involved TMZ resistance. Notably, more expressed higher-grade gliomas, negatively impacts patient survival regulates genes glucose metabolism.

Язык: Английский

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Loop Extrusion Machinery Impairments in Models and Disease

Cells, Год журнала: 2024, Номер 13(22), С. 1896 - 1896

Опубликована: Ноя. 17, 2024

Structural maintenance of chromosomes (SMC) complexes play a crucial role in organizing the three-dimensional structure chromatin, facilitating key processes such as gene regulation, DNA repair, and chromosome segregation. This review explores molecular mechanisms biological significance SMC-mediated loop extrusion complexes, including cohesin, condensins, SMC5/6, focusing on their structure, dynamic function during cell cycle, impact chromatin architecture. We discuss implications impairments machinery observed experimental models human diseases. Mutations affecting these are linked to various developmental disorders cancer, highlighting importance genome stability transcriptional regulation. Advances model systems genomic techniques have provided deeper insights into pathological roles SMC complex dysfunction, offering potential therapeutic avenues for associated

Язык: Английский

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Emerging roles of cohesin-STAG2 in cancer

Oncogene, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 29, 2024

Язык: Английский

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