Single-nucleus RNA sequencing reveals a preclinical model for the most common subtype of glioblastoma
Abstract Different glioblastoma (GBM) subtypes have been identified based on the tumor microenvironment (TME). The discovery of new therapies for these hard-to-treat tumors requires a thorough characterization of preclinical models, including their TME, to apply preclinical results to the most simil...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-04-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08092-x |
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| author | Laura García-Vicente María Martínez-Fernández Michael Borja Vanessa Tran Andrea Álvarez-Vázquez Raquel Flores-Hernández Yuxin Ding Raúl González-Sánchez Alejandro Granados Erin McGeever Yang-Joon Kim Angela Detweiler Honey Mekonen Sheryl Paul Angela O. Pisco Norma F. Neff Arantxa Tabernero |
| author_facet | Laura García-Vicente María Martínez-Fernández Michael Borja Vanessa Tran Andrea Álvarez-Vázquez Raquel Flores-Hernández Yuxin Ding Raúl González-Sánchez Alejandro Granados Erin McGeever Yang-Joon Kim Angela Detweiler Honey Mekonen Sheryl Paul Angela O. Pisco Norma F. Neff Arantxa Tabernero |
| author_sort | Laura García-Vicente |
| collection | DOAJ |
| description | Abstract Different glioblastoma (GBM) subtypes have been identified based on the tumor microenvironment (TME). The discovery of new therapies for these hard-to-treat tumors requires a thorough characterization of preclinical models, including their TME, to apply preclinical results to the most similar GBM subtype. Using single-nucleus RNA sequencing (snRNA-seq), we characterized the tumor and TME in an immunocompetent mouse model with intracranially implanted GBM stem cells at different stages and treatments. Visium spatial transcriptomics confirmed the location of annotated cells. This model exhibits GBM targets related to integration into neural circuits - Grik2, Nlgn3, Gap43 or Kcnn4-, immunoevasion - Nt5e, Cd274 or Irf8- and immunosuppression - Csf1r, Arg1, Mrc1 and Tgfb1. The landscape of cytokines, checkpoint ligands and receptors uncovered Mrc1, PD-L1, TIM-3 or B7-H3, among the immunotherapy targets that can be addressed in this model. The comparison with human GBMs unveiled crucial similarities with TMEMed GBM, the most frequent subtype. |
| format | Article |
| id | doaj-art-e2f6f106d54046b6b286eb5b91b7e5e9 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-e2f6f106d54046b6b286eb5b91b7e5e92025-08-20T03:52:23ZengNature PortfolioCommunications Biology2399-36422025-04-018111910.1038/s42003-025-08092-xSingle-nucleus RNA sequencing reveals a preclinical model for the most common subtype of glioblastomaLaura García-Vicente0María Martínez-Fernández1Michael Borja2Vanessa Tran3Andrea Álvarez-Vázquez4Raquel Flores-Hernández5Yuxin Ding6Raúl González-Sánchez7Alejandro Granados8Erin McGeever9Yang-Joon Kim10Angela Detweiler11Honey Mekonen12Sheryl Paul13Angela O. Pisco14Norma F. Neff15Arantxa Tabernero16Neuroscience Institute of Castile-Leon (INCYL), iBRAINS-IN-CyL, Department of Biochemistry and Molecular Biology, Biomedical Research Institute of Salamanca (IBSAL), University of SalamancaNeuroscience Institute of Castile-Leon (INCYL), iBRAINS-IN-CyL, Department of Biochemistry and Molecular Biology, Biomedical Research Institute of Salamanca (IBSAL), University of SalamancaChan Zuckerberg BiohubChan Zuckerberg BiohubNeuroscience Institute of Castile-Leon (INCYL), iBRAINS-IN-CyL, Department of Biochemistry and Molecular Biology, Biomedical Research Institute of Salamanca (IBSAL), University of SalamancaNeuroscience Institute of Castile-Leon (INCYL), iBRAINS-IN-CyL, Department of Biochemistry and Molecular Biology, Biomedical Research Institute of Salamanca (IBSAL), University of SalamancaNeuroscience Institute of Castile-Leon (INCYL), iBRAINS-IN-CyL, Department of Biochemistry and Molecular Biology, Biomedical Research Institute of Salamanca (IBSAL), University of SalamancaNeuroscience Institute of Castile-Leon (INCYL), iBRAINS-IN-CyL, Department of Biochemistry and Molecular Biology, Biomedical Research Institute of Salamanca (IBSAL), University of SalamancaChan Zuckerberg BiohubChan Zuckerberg BiohubChan Zuckerberg BiohubChan Zuckerberg BiohubChan Zuckerberg BiohubChan Zuckerberg BiohubChan Zuckerberg BiohubChan Zuckerberg BiohubNeuroscience Institute of Castile-Leon (INCYL), iBRAINS-IN-CyL, Department of Biochemistry and Molecular Biology, Biomedical Research Institute of Salamanca (IBSAL), University of SalamancaAbstract Different glioblastoma (GBM) subtypes have been identified based on the tumor microenvironment (TME). The discovery of new therapies for these hard-to-treat tumors requires a thorough characterization of preclinical models, including their TME, to apply preclinical results to the most similar GBM subtype. Using single-nucleus RNA sequencing (snRNA-seq), we characterized the tumor and TME in an immunocompetent mouse model with intracranially implanted GBM stem cells at different stages and treatments. Visium spatial transcriptomics confirmed the location of annotated cells. This model exhibits GBM targets related to integration into neural circuits - Grik2, Nlgn3, Gap43 or Kcnn4-, immunoevasion - Nt5e, Cd274 or Irf8- and immunosuppression - Csf1r, Arg1, Mrc1 and Tgfb1. The landscape of cytokines, checkpoint ligands and receptors uncovered Mrc1, PD-L1, TIM-3 or B7-H3, among the immunotherapy targets that can be addressed in this model. The comparison with human GBMs unveiled crucial similarities with TMEMed GBM, the most frequent subtype.https://doi.org/10.1038/s42003-025-08092-x |
| spellingShingle | Laura García-Vicente María Martínez-Fernández Michael Borja Vanessa Tran Andrea Álvarez-Vázquez Raquel Flores-Hernández Yuxin Ding Raúl González-Sánchez Alejandro Granados Erin McGeever Yang-Joon Kim Angela Detweiler Honey Mekonen Sheryl Paul Angela O. Pisco Norma F. Neff Arantxa Tabernero Single-nucleus RNA sequencing reveals a preclinical model for the most common subtype of glioblastoma Communications Biology |
| title | Single-nucleus RNA sequencing reveals a preclinical model for the most common subtype of glioblastoma |
| title_full | Single-nucleus RNA sequencing reveals a preclinical model for the most common subtype of glioblastoma |
| title_fullStr | Single-nucleus RNA sequencing reveals a preclinical model for the most common subtype of glioblastoma |
| title_full_unstemmed | Single-nucleus RNA sequencing reveals a preclinical model for the most common subtype of glioblastoma |
| title_short | Single-nucleus RNA sequencing reveals a preclinical model for the most common subtype of glioblastoma |
| title_sort | single nucleus rna sequencing reveals a preclinical model for the most common subtype of glioblastoma |
| url | https://doi.org/10.1038/s42003-025-08092-x |
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