Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states
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-nucle...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-38186-1 |
| _version_ | 1797832031336398848 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Osama Al-Dalahmah |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T14:01:12Z |
| format | Article |
| id | doaj.art-84706af8be0f4cffa61c89d018e75e54 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-09T14:01:12Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-84706af8be0f4cffa61c89d018e75e542023-05-07T11:17:21ZengNature PortfolioNature Communications2041-17232023-05-0114111810.1038/s41467-023-38186-1Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue statesOsama Al-Dalahmah0Michael G. Argenziano1Adithya Kannan2Aayushi Mahajan3Julia Furnari4Fahad Paryani5Deborah Boyett6Akshay Save7Nelson Humala8Fatima Khan9Juncheng Li10Hong Lu11Yu Sun12John F. Tuddenham13Alexander R. Goldberg14Athanassios Dovas15Matei A. Banu16Tejaswi Sudhakar17Erin Bush18Andrew B. Lassman19Guy M. McKhann20Brian J. A. Gill21Brett Youngerman22Michael B. Sisti23Jeffrey N. Bruce24Peter A. Sims25Vilas Menon26Peter Canoll27Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons (VP&S)Department of Neurological Surgery, Columbia University Vagelos College of Physicians and Surgeons (VP&S)Department of Neurological Surgery, Columbia University Vagelos College of Physicians and Surgeons (VP&S)Department of Neurological Surgery, Columbia University Vagelos College of Physicians and Surgeons (VP&S)Department of Neurological Surgery, Columbia University Vagelos College of Physicians and Surgeons (VP&S)Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons (VP&S)Department of Neurological Surgery, Columbia University Vagelos College of Physicians and Surgeons (VP&S)Department of Neurological Surgery, Columbia University Vagelos College of Physicians and Surgeons (VP&S)Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical CenterDepartment of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons (VP&S)Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons (VP&S)Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons (VP&S)Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons (VP&S)Department of Systems Biology, Columbia University Vagelos College of Physicians and Surgeons (VP&S)Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons (VP&S)Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons (VP&S)Department of Neurological Surgery, Columbia University Vagelos College of Physicians and Surgeons (VP&S)Department of Neurological Surgery, Columbia University Vagelos College of Physicians and Surgeons (VP&S)Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons (VP&S)Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical CenterHerbert Irving Comprehensive Cancer Center, Columbia University Irving Medical CenterHerbert Irving Comprehensive Cancer Center, Columbia University Irving Medical CenterHerbert Irving Comprehensive Cancer Center, Columbia University Irving Medical CenterHerbert Irving Comprehensive Cancer Center, Columbia University Irving Medical CenterHerbert Irving Comprehensive Cancer Center, Columbia University Irving Medical CenterHerbert Irving Comprehensive Cancer Center, Columbia University Irving Medical CenterDepartment of Neurology, Columbia University Vagelos College of Physicians and Surgeons (VP&S)Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons (VP&S)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.https://doi.org/10.1038/s41467-023-38186-1 |
| spellingShingle | 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 Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states Nature Communications |
| title | Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states |
| title_full | Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states |
| title_fullStr | Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states |
| title_full_unstemmed | Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states |
| title_short | Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states |
| title_sort | re convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states |
| url | https://doi.org/10.1038/s41467-023-38186-1 |
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