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

• DOI: 10.1016/j.xcrm.2023.101249
• Publication Date: 2023-10-25T14:31:54Z
• Authors: Enrique Blanco-Ca...; Ashwin Narayanan; Inmaculada Hernandez; Juan C. Nieto; Marc Elosua-Bayes; Xueyuan Sun; Claudia Schmidt; Necmettin Pamir; Koray Özduman; Christel Herold-M...; Francesca Pagani; Manuela Cominelli; Julian Taranda; Wolfgang Wick; Andreas von Deimling; Pietro Luigi Poliani; Michael Rehli; Matthias Schlesner; Holger Heyn; Şevin Turcan
• Keywords: Isocitrate dehydrogenase; Tumor progression; Brain tumor

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 ATAC sequencing to compare the molecular heterogeneity of these glioma subtypes. In addition astrocyte-like, oligodendrocyte progenitor-like, cycling tumor subpopulations, a population enriched for ribosomal genes translation elongation factors primarily present oligodendrogliomas. Longitudinal analysis astrocytomas indicates that proportion subpopulations remains stable recurrent tumors. Analysis tumor-associated microglia/macrophages (TAMs) reveals significant differences between oligodendrogliomas, harboring inflammatory TAMs expressing phosphorylated STAT1, as confirmed by immunohistochemistry. Furthermore, inferred receptor-ligand interactions may contribute TAM state diversity. Overall, our study sheds light on distinct populations, heterogeneity, TAM-tumor subtypes, relative stability astrocytomas.