| Autor: |
Osama Al-Dalahmah, Michael G. Argenziano, Adithya Kannan, Aayushi Mahajan, Julia Furnari, Fahad Paryani, Deborah Boyett, Akshay Save, Nelson Humala, Fatima Khan, Juncheng Li, Hong Lu, Yu Sun, John F. Tuddenham, Alexander R. Goldberg, Athanassios Dovas, Matei A. Banu, Tejaswi Sudhakar, Erin Bush, Andrew B. Lassman, Guy M. McKhann, Brian J. A. Gill, Brett Youngerman, Michael B. Sisti, Jeffrey N. Bruce, Peter A. Sims, Vilas Menon, Peter Canoll |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 14, Iss 1, Pp 1-18 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-023-38186-1 |
| Popis: |
Abstract Glioblastoma (GBM) diffusely infiltrates the brain and intermingles with non-neoplastic brain cells, including astrocytes, neurons and microglia/myeloid cells. This complex mixture of cell types forms the biological context for therapeutic response and tumor recurrence. We used single-nucleus RNA sequencing and spatial transcriptomics to determine the cellular composition and transcriptional states in primary and recurrent glioma and identified three compositional ‘tissue-states’ defined by cohabitation patterns between specific subpopulations of neoplastic and non-neoplastic brain cells. These tissue-states correlated with radiographic, histopathologic, and prognostic features and were enriched in distinct metabolic pathways. Fatty acid biosynthesis was enriched in the tissue-state defined by the cohabitation of astrocyte-like/mesenchymal glioma cells, reactive astrocytes, and macrophages, and was associated with recurrent GBM and shorter survival. Treating acute slices of GBM with a fatty acid synthesis inhibitor depleted the transcriptional signature of this pernicious tissue-state. These findings point to therapies that target interdependencies in the GBM microenvironment. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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Full text from SpringerLink