% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Man:293327, author = {K. H. Man$^*$ and Y. Wu and Z. Gao and A.-S. Spreng$^*$ and S. J. E. Keding$^*$ and J. Mangei$^*$ and P. Boskovic$^*$ and J.-P. Mallm$^*$ and H.-K. Liu$^*$ and C. D. Imbusch$^*$ and P. Lichter$^*$ and B. Radlwimmer$^*$}, title = {{SOX}10 mediates glioblastoma cell-state plasticity.}, journal = {EMBO reports}, volume = {25}, number = {11}, issn = {1469-221X}, address = {Hoboken, NJ [u.a.]}, publisher = {Wiley}, reportid = {DKFZ-2024-01877}, pages = {5113-5140}, year = {2024}, note = {#EA:B060#LA:B060# / 2024 Nov;25(11):5113-5140}, abstract = {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.}, keywords = {SOX10 (Other) / Glioblastoma (Other) / Phenotypic Plasticity (Other) / Therapy Resistance (Other) / Tumor Cell Quiescence (Other)}, cin = {B060 / B330 / A240 / W192}, ddc = {570}, cid = {I:(DE-He78)B060-20160331 / I:(DE-He78)B330-20160331 / I:(DE-He78)A240-20160331 / I:(DE-He78)W192-20160331}, pnm = {312 - Funktionelle und strukturelle Genomforschung (POF4-312)}, pid = {G:(DE-HGF)POF4-312}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:39285246}, doi = {10.1038/s44319-024-00258-8}, url = {https://inrepo02.dkfz.de/record/293327}, }