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000293327 1001_ $$0P:(DE-He78)54ffbd220f4f40801144e564197dd3d4$$aMan, Ka Hou$$b0$$eFirst author$$udkfz
000293327 245__ $$aSOX10 mediates glioblastoma cell-state plasticity.
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000293327 520__ $$aPhenotypic plasticity is a cause of glioblastoma therapy failure. We previously showed that suppressing the oligodendrocyte-lineage regulator SOX10 promotes glioblastoma progression. Here, we analyze SOX10-mediated phenotypic plasticity and exploit it for glioblastoma therapy design. We show that low SOX10 expression is linked to neural stem-cell (NSC)-like glioblastoma cell states and is a consequence of temozolomide treatment in animal and cell line models. Single-cell transcriptome profiling of Sox10-KD tumors indicates that Sox10 suppression is sufficient to induce tumor progression to an aggressive NSC/developmental-like phenotype, including a quiescent NSC-like cell population. The quiescent NSC state is induced by temozolomide and Sox10-KD and reduced by Notch pathway inhibition in cell line models. Combination treatment using Notch and HDAC/PI3K inhibitors extends the survival of mice carrying Sox10-KD tumors, validating our experimental therapy approach. In summary, SOX10 suppression mediates glioblastoma progression through NSC/developmental cell-state transition, including the induction of a targetable quiescent NSC state. This work provides a rationale for the design of tumor therapies based on single-cell phenotypic plasticity analysis.
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000293327 650_7 $$2Other$$aSOX10
000293327 650_7 $$2Other$$aGlioblastoma
000293327 650_7 $$2Other$$aPhenotypic Plasticity
000293327 650_7 $$2Other$$aTherapy Resistance
000293327 650_7 $$2Other$$aTumor Cell Quiescence
000293327 7001_ $$aWu, Yonghe$$b1
000293327 7001_ $$aGao, Zhenjiang$$b2
000293327 7001_ $$0P:(DE-He78)c4c258d44a86b1ab0d1c5d7370a4a916$$aSpreng, Anna-Sophie$$b3$$udkfz
000293327 7001_ $$0P:(DE-He78)4009b389a34f8d3f41368959e7fd8e6a$$aKeding, Sigrun Johanna Elisabeth$$b4
000293327 7001_ $$0P:(DE-He78)1bf78749dde0284a02c44a5153fba925$$aMangei, Jasmin$$b5
000293327 7001_ $$0P:(DE-He78)843808e53ce583be326cf75564db3bdd$$aBoskovic, Pavle$$b6
000293327 7001_ $$0P:(DE-He78)697cb039ca08f3b7e5a2a52dbf020b46$$aMallm, Jan-Philipp$$b7$$udkfz
000293327 7001_ $$0P:(DE-He78)76aeb2431f7458c9261e69c5420390c6$$aLiu, Hai-Kun$$b8$$udkfz
000293327 7001_ $$00000-0003-4920-551X$$aImbusch, Charles D$$b9
000293327 7001_ $$0P:(DE-He78)e13b4363c5fe858044ef8a39c02c870c$$aLichter, Peter$$b10$$udkfz
000293327 7001_ $$0P:(DE-He78)d1939d434dd885fad08106329e3db719$$aRadlwimmer, Bernhard$$b11$$eLast author$$udkfz
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