METTL7B is an essential epigenetic regulator of lineage specification in glioblastoma [scRNAseq]

Glioblastomas are the most common malignant brain tumours in adults; they are highly aggressive, heterogeneous and plastic. We have identified METTL7B as an essential regulator of lineage specification in glioblastoma, with impact on both tumour size and invasiveness in in vivo models. Single cell transcriptomic analysis of these tumours and of cerebral organoids derived from expanded potential stem cells overexpressing METTL7B identified a regulatory role for the gene in the neural stem cells to astrocyte differentiation trajectory. Mechanistically, METTL7B downregulates the expression of key neuronal differentiation players, including SALL2, via DNA methylation and post-translational modifications of histone marks. 1) scRNAseq of GIC xenografts, with scrambled or anti-METTL7B shRNA 2) scRNAseq of control (PK/PK-Cas9) COs vs METTL7B-OE COs