%0 Journal Article
%A Man, Ka Hou
%A Wu, Yonghe
%A Gao, Zhenjiang
%A Spreng, Anna-Sophie
%A Keding, Sigrun Johanna Elisabeth
%A Mangei, Jasmin
%A Boskovic, Pavle
%A Mallm, Jan-Philipp
%A Liu, Hai-Kun
%A Imbusch, Charles D
%A Lichter, Peter
%A Radlwimmer, Bernhard
%T SOX10 mediates glioblastoma cell-state plasticity.
%J EMBO reports
%V 25
%N 11
%@ 1469-221X
%C Hoboken, NJ [u.a.]
%I Wiley
%M DKFZ-2024-01877
%P 5113-5140
%D 2024
%Z #EA:B060#LA:B060# / 2024 Nov;25(11):5113-5140
%X Phenotypic plasticity is a cause of glioblastoma therapy failure. We previously showed that suppressing the oligodendrocyte-lineage regulator SOX10 promotes glioblastoma progression. Here, we analyze SOX10-mediated phenotypic plasticity and exploit it for glioblastoma therapy design. We show that low SOX10 expression is linked to neural stem-cell (NSC)-like glioblastoma cell states and is a consequence of temozolomide treatment in animal and cell line models. Single-cell transcriptome profiling of Sox10-KD tumors indicates that Sox10 suppression is sufficient to induce tumor progression to an aggressive NSC/developmental-like phenotype, including a quiescent NSC-like cell population. The quiescent NSC state is induced by temozolomide and Sox10-KD and reduced by Notch pathway inhibition in cell line models. Combination treatment using Notch and HDAC/PI3K inhibitors extends the survival of mice carrying Sox10-KD tumors, validating our experimental therapy approach. In summary, SOX10 suppression mediates glioblastoma progression through NSC/developmental cell-state transition, including the induction of a targetable quiescent NSC state. This work provides a rationale for the design of tumor therapies based on single-cell phenotypic plasticity analysis.
%K SOX10 (Other)
%K Glioblastoma (Other)
%K Phenotypic Plasticity (Other)
%K Therapy Resistance (Other)
%K Tumor Cell Quiescence (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39285246
%R 10.1038/s44319-024-00258-8
%U https://inrepo02.dkfz.de/record/293327