Tumor heterogeneity and tumor-microglia interactions in primary and recurrent IDH1-mutant gliomas
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- dc.contributor.author Blanco-Carmona, Enrique
- dc.contributor.author Narayanan, Ashwin
- dc.contributor.author Hernandez, Inmaculada
- dc.contributor.author Nieto, Juan C.
- dc.contributor.author Elosua-Bayés, Marc
- dc.contributor.author Sun, Xueyuan
- dc.contributor.author Schmidt, Claudia
- dc.contributor.author Pamir, Necmettin
- dc.contributor.author Özduman, Koray
- dc.contributor.author Herold-Mende, Christel
- dc.contributor.author Pagani, Francesca
- dc.contributor.author Cominelli, Manuela
- dc.contributor.author Taranda, Julian
- dc.contributor.author Wick, Wolfgang
- dc.contributor.author von Deimling, Andreas
- dc.contributor.author Poliani, Pietro Luigi
- dc.contributor.author Rehli, Michael
- dc.contributor.author Schlesner, Matthias
- dc.contributor.author Heyn, Holger
- dc.contributor.author Turcan, Sevin
- dc.date.accessioned 2024-02-12T06:36:48Z
- dc.date.available 2024-02-12T06:36:48Z
- dc.date.issued 2023
- dc.description.abstract The isocitrate dehydrogenase (IDH) gene is recurrently mutated in adult diffuse gliomas. IDH-mutant gliomas are categorized into oligodendrogliomas and astrocytomas, each with unique pathological features. Here, we use single-nucleus RNA and ATAC sequencing to compare the molecular heterogeneity of these glioma subtypes. In addition to astrocyte-like, oligodendrocyte progenitor-like, and cycling tumor subpopulations, a tumor population enriched for ribosomal genes and translation elongation factors is primarily present in oligodendrogliomas. Longitudinal analysis of astrocytomas indicates that the proportion of tumor subpopulations remains stable in recurrent tumors. Analysis of tumor-associated microglia/macrophages (TAMs) reveals significant differences between oligodendrogliomas, with astrocytomas harboring inflammatory TAMs expressing phosphorylated STAT1, as confirmed by immunohistochemistry. Furthermore, inferred receptor-ligand interactions between tumor subpopulations and TAMs may contribute to TAM state diversity. Overall, our study sheds light on distinct tumor populations, TAM heterogeneity, TAM-tumor interactions in IDH-mutant glioma subtypes, and the relative stability of tumor subpopulations in recurrent astrocytomas.
- dc.format.mimetype application/pdf
- dc.identifier.citation Blanco-Carmona E, Narayanan A, Hernandez I, Nieto JC, Elosua-Bayes M, Sun X, Schmidt C, Pamir N, Özduman K, Herold-Mende C, Pagani F, Cominelli M, Taranda J, Wick W, von Deimling A, Poliani PL, Rehli M, Schlesner M, Heyn H, Turcan S. Tumor heterogeneity and tumor-microglia interactions in primary and recurrent IDH1-mutant gliomas. Cell Rep Med. 2023 Nov 21;4(11):101249. DOI: 10.1016/j.xcrm.2023.101249
- dc.identifier.doi http://dx.doi.org/10.1016/j.xcrm.2023.101249
- dc.identifier.issn 2666-3791
- dc.identifier.uri http://hdl.handle.net/10230/59061
- dc.language.iso eng
- dc.publisher Elsevier
- dc.relation.ispartof Cell Rep Med. 2023 Nov 21;4(11):101249
- dc.rights © 2023 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
- dc.subject.keyword IDH mutation
- dc.subject.keyword Astrocytoma
- dc.subject.keyword Bone-marrow-derived macrophages
- dc.subject.keyword Glioma
- dc.subject.keyword Microglia
- dc.subject.keyword Oligodendroglioma
- dc.subject.keyword Recurrent glioma
- dc.subject.keyword snATAC-seq
- dc.subject.keyword snRNA-seq
- dc.subject.keyword Tumor microenvironment
- dc.title Tumor heterogeneity and tumor-microglia interactions in primary and recurrent IDH1-mutant gliomas
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion