Glioblastoma-cortical organoids recapitulate cell state heterogeneity and intercellular transfer
Glioblastoma is characterized by heterogeneous malignant cells that are functionally integrated within the neuroglial microenvironment. Here, we model this ecosystem by growing glioblastoma into long-term cultured human cortical organoids that contain the major neuroglial cell types found in the cer...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Association for Cancer Research
2024
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| Online Access: | https://hdl.handle.net/1721.1/157902 |
| _version_ | 1824458333036216320 |
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| author | Mangena, Vamsi Chanoch-Myers, Rony Sartore, Rafaela Paulsen, Bruna Gritsch, Simon Weisman, Hannah Hara, Toshiro Breakefield, Xandra O Breyne, Koen Regev, Aviv Chung, Kwanghun Arlotta, Paola Tirosh, Itay Suva, Mario L |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Mangena, Vamsi Chanoch-Myers, Rony Sartore, Rafaela Paulsen, Bruna Gritsch, Simon Weisman, Hannah Hara, Toshiro Breakefield, Xandra O Breyne, Koen Regev, Aviv Chung, Kwanghun Arlotta, Paola Tirosh, Itay Suva, Mario L |
| author_sort | Mangena, Vamsi |
| collection | MIT |
| description | Glioblastoma is characterized by heterogeneous malignant cells that are functionally integrated within the neuroglial microenvironment. Here, we model this ecosystem by growing glioblastoma into long-term cultured human cortical organoids that contain the major neuroglial cell types found in the cerebral cortex. Single-cell RNA-seq analysis suggests that, compared to matched gliomasphere models, glioblastoma cortical organoids (GCO) more faithfully recapitulate the diversity and expression programs of malignant cell states found in patient tumors. Additionally, we observe widespread transfer of glioblastoma transcripts and GFP proteins to non-malignant cells in the organoids. Mechanistically, this transfer involves extracellular vesicles and is biased towards defined glioblastoma cell states and astroglia cell types. These results extend previous glioblastoma-organoid modeling efforts and suggest widespread intercellular transfer in the glioblastoma neuroglial microenvironment. |
| first_indexed | 2025-02-19T04:24:13Z |
| format | Article |
| id | mit-1721.1/157902 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2025-02-19T04:24:13Z |
| publishDate | 2024 |
| publisher | American Association for Cancer Research |
| record_format | dspace |
| spelling | mit-1721.1/1579022025-01-05T04:26:05Z Glioblastoma-cortical organoids recapitulate cell state heterogeneity and intercellular transfer Mangena, Vamsi Chanoch-Myers, Rony Sartore, Rafaela Paulsen, Bruna Gritsch, Simon Weisman, Hannah Hara, Toshiro Breakefield, Xandra O Breyne, Koen Regev, Aviv Chung, Kwanghun Arlotta, Paola Tirosh, Itay Suva, Mario L Massachusetts Institute of Technology. Department of Chemical Engineering Glioblastoma is characterized by heterogeneous malignant cells that are functionally integrated within the neuroglial microenvironment. Here, we model this ecosystem by growing glioblastoma into long-term cultured human cortical organoids that contain the major neuroglial cell types found in the cerebral cortex. Single-cell RNA-seq analysis suggests that, compared to matched gliomasphere models, glioblastoma cortical organoids (GCO) more faithfully recapitulate the diversity and expression programs of malignant cell states found in patient tumors. Additionally, we observe widespread transfer of glioblastoma transcripts and GFP proteins to non-malignant cells in the organoids. Mechanistically, this transfer involves extracellular vesicles and is biased towards defined glioblastoma cell states and astroglia cell types. These results extend previous glioblastoma-organoid modeling efforts and suggest widespread intercellular transfer in the glioblastoma neuroglial microenvironment. 2024-12-20T19:50:26Z 2024-12-20T19:50:26Z 2024-10-07 2024-12-20T19:37:16Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/157902 Vamsi Mangena, Rony Chanoch-Myers, Rafaela Sartore, Bruna Paulsen, Simon Gritsch, Hannah Weisman, Toshiro Hara, Xandra O. Breakefield, Koen Breyne, Aviv Regev, Kwanghun Chung, Paola Arlotta, Itay Tirosh, Mario L. Suva; Glioblastoma-cortical organoids recapitulate cell state heterogeneity and intercellular transfer. Cancer Discov 2024. en 10.1158/2159-8290.cd-23-1336 Cancer Discovery Creative Commons Attribution-NonCommercial-NoDerivs https://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf American Association for Cancer Research American Association for Cancer Research |
| spellingShingle | Mangena, Vamsi Chanoch-Myers, Rony Sartore, Rafaela Paulsen, Bruna Gritsch, Simon Weisman, Hannah Hara, Toshiro Breakefield, Xandra O Breyne, Koen Regev, Aviv Chung, Kwanghun Arlotta, Paola Tirosh, Itay Suva, Mario L Glioblastoma-cortical organoids recapitulate cell state heterogeneity and intercellular transfer |
| title | Glioblastoma-cortical organoids recapitulate cell state heterogeneity and intercellular transfer |
| title_full | Glioblastoma-cortical organoids recapitulate cell state heterogeneity and intercellular transfer |
| title_fullStr | Glioblastoma-cortical organoids recapitulate cell state heterogeneity and intercellular transfer |
| title_full_unstemmed | Glioblastoma-cortical organoids recapitulate cell state heterogeneity and intercellular transfer |
| title_short | Glioblastoma-cortical organoids recapitulate cell state heterogeneity and intercellular transfer |
| title_sort | glioblastoma cortical organoids recapitulate cell state heterogeneity and intercellular transfer |
| url | https://hdl.handle.net/1721.1/157902 |
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