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Tumor heterogeneity and tumor-microglia interactions in primary and recurrent IDH1-mutant gliomas

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...

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Main Authors: Blanco Carmona, Enrique (Author) , Narayanan, Ashwin (Author) , Hernandez, Inmaculada (Author) , Nieto, Juan C. (Author) , Elosua-Bayes, Marc (Author) , Sun, Xueyuan (Author) , Schmidt, Claudia (Author) , Pamir, Necmettin (Author) , Ozduman, Koray (Author) , Herold-Mende, Christel (Author) , Pagani, Francesca (Author) , Cominelli, Manuela (Author) , Taranda, Julian (Author) , Wick, Wolfgang (Author) , Deimling, Andreas von (Author) , Poliani, Pietro Luigi (Author) , Rehli, Michael (Author) , Schlesner, Matthias (Author) , Heyn, Holger (Author) , Turcan, S̨evin (Author)
Format: Article (Journal)
Language:English
Published: 21 November 2023
In: Cell reports. Medicine
Year: 2023, Volume: 4, Issue: 11, Pages: 1-20
ISSN:2666-3791
DOI:10.1016/j.xcrm.2023.101249
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.xcrm.2023.101249
Verlag, lizenzpflichtig, Volltext: https://www.webofscience.com/api/gateway?GWVersion=2&SrcAuth=DOISource&SrcApp=WOS&KeyAID=10.1016%2Fj.xcrm.2023.101249&DestApp=DOI&SrcAppSID=EUW1ED0DEDAXm39fhMw1G6Q5fO9E4&SrcJTitle=CELL+REPORTS+MEDICINE&DestDOIRegistrantName=Elsevier
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Author Notes:Enrique Blanco-Carmona, Ashwin Narayanan, Inmaculada Hernandez, Juan C. Nieto, Marc Elosua-Bayes, Xueyuan Sun, Claudia Schmidt, Necmettin Pamir, Koray Ozduman, Christel Herold-Mende, Francesca Pagani, Manuela Cominelli, Julian Taranda, Wolfgang Wick, Andreas von Deimling, Pietro Luigi Poliani, Michael Rehli, Matthias Schlesner, Holger Heyn, and Sevin Turcan
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Summary: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.
Item Description:Gesehen am 04.11.2024
Physical Description:Online Resource
ISSN:2666-3791
DOI:10.1016/j.xcrm.2023.101249

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