2026-09-15T16:58:00Zhttps://gredos.usal.es/oai/request

oai:gredos.usal.es:10366/1676382026-03-25T12:20:52Zcom_10366_4613com_10366_4576com_10366_3823col_10366_4616

García Vicente, Laura Martínez Fernández, María Borja, Michael Tran, Vanessa Álvarez Vázquez, Andrea Flores Hernández, Raquel Ding, Yuxin González Sánchez, Raúl Granados, Alejandro McGeever, Erin Kim, Yang-Joon Detweiler, Angela Mekonen, Honey Paul, Sheryl Pisco, Angela O. Neff, Norma F. Tabernero Urbieta, María Aránzazu 2025-11-04T13:59:28Z 2025-11-04T13:59:28Z 2025-04-28 García-Vicente, L., Martínez-Fernández, M., Borja, M., Tran, V., Álvarez-Vázquez, A., Flores-Hernández, R., Ding, Y., González-Sánchez, R., Granados, A., McGeever, E., Kim, Y.-J., Detweiler, A., Mekonen, H., Paul, S., Pisco, A. O., Neff, N. F., y Tabernero, A. (2025). Single-nucleus RNA sequencing reveals a preclinical model for the most common subtype of glioblastoma. Communications Biology, 8(1), 1-19. https://doi.org/10.1038/s42003-025-08092-x http://hdl.handle.net/10366/167638 10.1038/s42003-025-08092-x 2399-3642 [EN] 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. This work was funded by the grants FEDER PID2021-128549OB-I00 (Arantxa Tabernero) funded by MCIN/AEI/ 10.13039/501100011033 and “ERDF A way of making Europe,” PDC2022-133652-I00 (Arantxa Tabernero) funded by MCIN/AEI/ 10.13039/501100011033 and “European Union NextGenerationEU/PRTR”, SA125P20 and SA212P24 (Arantxa Tabernero), CLU-2023-1-01(Arantxa Tabernero) funded by FEDER and Junta de Castilla y León, and grants from Chan Zuckerberg Biohub SF (Norma Neff). L. García-Vicente was supported by the Spanish Ministerio de Universidades. M. Martínez-Fernández, A. Álvarez-Vázquez and R. Flores-Hernández were fellowship recipients from the Junta de Castilla y León and the European Social Fund. Y. Ding was a “Programa Investigo” fellowship recipient and R. González-Sánchez was a technician from the Junta de Castilla y León, Servicio Público de Empleo Estatal and the European Social Fund, NextGenerationEU. We are grateful to Spyros Darmanis and Ashley Byrne for initial support and guidance to the project. We thank T. del Rey for technical assistance. eng Springer Nature Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Animals Brain Neoplasms Cell Line Tumor Disease Models Animal Gene Expression Regulation Neoplastic Glioblastoma Humans Mice Sequence Analysis, RNA Single-Cell Analysis Tumor Microenvironment 3201.01 Oncología 3207.13 Oncología 2407.01 Cultivo Celular Single-nucleus RNA sequencing reveals a preclinical model for the most common subtype of glioblastoma info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://doi.org/10.1038/s42003-025-08092-x FEDER PID2021-128549OB-I00 MCIN/AEI/ 10.13039/501100011033 PDC2022-133652-I00 MCIN/AEI/ 10.13039/501100011033 SA125P20 SA212P24 CLU-2023-1-01 Communications Biology 8 1