Fig. 1

GSK3 inhibition disturbs IDH1^R132H induced transcriptional programs. A Experimental Design. Chemical inhibition of WNT/GSK3 (CHIR99021), TGF-β (Repsox) and γ-secretase (YO-01027) in immortalized conditional IDH1^R132H astrocytes. B Flow cytometry after treatment with CHIR99021, Repsox and YO-01027 showed significantly changed expression of LGG-associated marker L1CAM (n = 2 biological and 3 technical replicates each). C Multidimensional scaling analysis of RNA-seq data showing segregation of CHIR99021- and Repsox-treated samples from control samples. D Heatmaps of all differentially expressed genes upon treatment with CHIR99021, Repsox, or YO-01027, showing most profound transcriptional reshaping after GSK3 inhibition. E Distribution of up- and downregulated DEGs after GSK3 inhibition, showing a higher fraction of downregulated genes, including those relevantin IDH^mut gliomas. F Gene expression of L1CAM and GSK3B is positively correlated in IDH^mut glioma patient cohorts (R = 0.29, p = 0.0017) (source: CGGA mRNA dataset, only primary IDH^mut glioma from cases included). Correlation was determined with Pearson’s correlation test. G GSK3B is significantly overexpressed in IDH^mut gliomas compared to IDH^wt gliomas (Wilcoxon test, p = 5.9 × 10^− 7; source: CGGA)