Academic Journal
Hypoxia drives shared and distinct transcriptomic changes in two invasive glioma stem cell lines
| Title: | Hypoxia drives shared and distinct transcriptomic changes in two invasive glioma stem cell lines |
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| Authors: | Valerie J. Marallano, Mary E. Ughetta, Rut Tejero, Sidhanta Nanda, Rohana Ramalingam, Lauren Stalbow, Anirudh Sattiraju, Yong Huang, Aarthi Ramakrishnan, Li Shen, Alexandre Wojcinski, Santosh Kesari, Hongyan Zou, Alexander M. Tsankov, Roland H. Friedel |
| Source: | Scientific Reports, Vol 14, Iss 1, Pp 1-12 (2024) |
| Publisher Information: | Nature Portfolio, 2024. |
| Publication Year: | 2024 |
| Collection: | LCC:Medicine LCC:Science |
| Subject Terms: | Glioblastoma, glioma, hypoxia, Medicine, Science |
| More Details: | Abstract Glioblastoma (GBM) is the most common primary malignant cancer of the central nervous system. Insufficient oxygenation (hypoxia) has been linked to GBM invasion and aggression, leading to poor patient outcomes. Hypoxia induces gene expression for cellular adaptations. However, GBM is characterized by high intertumoral (molecular subtypes) and intratumoral heterogeneity (cell states), and it is not well understood to what extent hypoxia triggers patient-specific gene responses and cellular diversity in GBM. Here, we surveyed eight patient-derived GBM stem cell lines for invasion phenotypes in 3D culture, which identified two GBM lines showing increased invasiveness in response to hypoxia. RNA-seq analysis of the two patient GBM lines revealed a set of shared hypoxia response genes concerning glucose metabolism, angiogenesis, and autophagy, but also a large set of patient-specific hypoxia-induced genes featuring cell migration and anti-inflammation, highlighting intertumoral diversity of hypoxia responses in GBM. We further applied the Shared GBM Hypoxia gene signature to single cell RNA-seq datasets of glioma patients, which showed that hypoxic cells displayed a shift towards mesenchymal-like (MES) and astrocyte-like (AC) states. Interestingly, in response to hypoxia, tumor cells in IDH-mutant gliomas displayed a strong shift to the AC state, whereas tumor cells in IDH-wildtype gliomas mainly shifted to the MES state. This distinct hypoxia response of IDH-mutant gliomas may contribute to its more favorable prognosis. Our transcriptomic studies provide a basis for future approaches to better understand the diversity of hypoxic niches in gliomas. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-024-56102-5 |
| Access URL: | https://doaj.org/article/dd8338919ea04009b7ac965cd5a4e33e |
| Accession Number: | edsdoj.8338919ea04009b7ac965cd5a4e33e |
| Database: | Directory of Open Access Journals |
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| ISSN: | 20452322 |
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| DOI: | 10.1038/s41598-024-56102-5 |
| Published in: | Scientific Reports |
| Language: | English |