Related Experiment Video
Updated: Sep 13, 2025
A Human Glioblastoma Organotypic Slice Culture Model for Study of Tumor Cell Migration and Patient-specific Effects of Anti-Invasive Drugs
Published on: July 20, 2017
Single-Cell Transcriptomic Changes in Patient-Derived Glioma and U87 Glioblastoma Cell Cultures Infected with the
Dmitriy V Semenov1, Natalia S Vasileva1,2, Maxim E Menyailo3
1Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Lavrentyev Avenue, 8, Novosibirsk 630090, Russia.
Abstract:
Oncolytic virotherapy is a rapidly evolving approach to cancer treatment. Our group previously designed VV-GMCSF-Lact, a recombinant oncolytic vaccinia virus targeting solid tumors including gliomas. In this study, we used single-cell RNA sequencing to compare transcriptional responses in human glioma cells, non-malignant brain cells, and immortalized glioblastoma U87 MG cells following infection with this oncolytic virus. We found that proneural glioblastoma cells and microglia-like cells from patient-derived glioma cultures were the most susceptible to VV-GMCSF-Lact. Increased expressions of histones, translational regulators, and ribosomal proteins positively correlated with viral load at the transcript level. Furthermore, higher viral loads were accompanied by a large-scale downregulation of genes involved in mitochondrial translation, metabolism, and oxidative phosphorylation. Levels of early vaccinia virus transcripts are also positively correlated with infection intensity, suggesting that the fate of cells is determined at the early stage of infection.
Insights
This study reveals that proneural glioblastoma and microglia-like cells are most susceptible to the oncolytic virus VV-GMCSF-Lact. Early viral gene expression correlates with cell fate, impacting mitochondrial function and metabolism.
Area of Science:
- Oncology
- Virology
- Genomics
Background:
- Oncolytic virotherapy is an emerging cancer treatment strategy.
- Recombinant vaccinia virus VV-GMCSF-Lact was previously developed to target solid tumors like gliomas.
Purpose of the Study:
- To compare transcriptional responses in different human brain cells after infection with VV-GMCSF-Lact.
- To identify cell types and molecular pathways affected by oncolytic vaccinia virus infection.
Main Methods:
- Single-cell RNA sequencing was employed to analyze transcriptional changes.
- Human glioma cells, non-malignant brain cells, and U87 MG glioblastoma cells were infected with VV-GMCSF-Lact.
- Correlation analysis was performed between viral load and host gene expression.
Main Results:
- Proneural glioblastoma cells and microglia-like cells showed the highest susceptibility to VV-GMCSF-Lact.
- Increased expression of histone, translational, and ribosomal genes correlated with viral load.
- Downregulation of mitochondrial translation, metabolism, and oxidative phosphorylation genes was observed with higher viral loads.
- Early vaccinia virus transcript levels correlated with infection intensity.
Conclusions:
- Cellular susceptibility to VV-GMCSF-Lact varies, with proneural glioblastoma and microglia-like cells being most vulnerable.
- Viral infection significantly alters host cell gene expression, particularly affecting metabolic and translational pathways.
- Early viral gene expression may determine the ultimate fate of infected cells in oncolytic virotherapy.
More Related Videos
12:25Optimization of High Grade Glioma Cell Culture from Surgical Specimens for Use in Clinically Relevant Animal Models and 3D Immunochemistry
Published on: January 7, 2014
10:13Modeling Astrocytoma Pathogenesis In Vitro and In Vivo Using Cortical Astrocytes or Neural Stem Cells from Conditional, Genetically Engineered Mice
Published on: August 12, 2014