Our team explores molecular mechanisms underlying brain tumor heterogeneity. We are especially interested in Glioblastoma (GB) cell plasticity, a source of the extensive heterogeneity characterizing this devastating brain tumor. We notably explored epigenetic regulations varying between cancer cells assuming distinct phenotypes. This led among others to discover a novel signaling module that controls GB cell aggressiveness by coupling GABA metabolism and epigenetic regulations, as well as to identify ARNT2 as a core component of the transcription factor network regulating GB cell tumorigenicity (Acta Neuropathologica, 2017, 2018). Importantly, the relevance of our findings in the context of the human pathology was verified using patients’ tumor samples. Additional projects led, for example, to identify an anti-hypertensive drug as a compound toxic for GB cells with stem-like properties but sparing human neural stem cells (EMBO Mol Med, 2016). We now implement a systemic approach to identify metabolic modules that underlie the dynamic plasticity of GB cells within the patients' tumors. We recently developed and validated a novel strategy combining experimental “wet” biology with specific computational analyses of scRNA-seq, to uncover links between metabolic modules and GB cell functional states at the time of patients’ diagnosis. This strategy already resulted in revealing the key role of ELOVL2, an enzyme of the synthesis pathway of very long chain polyunsaturated fatty acids, in maintaining GB cell aggressiveness (Acta Neuropathologica Comm, 2019). It also revealed the enzyme of the cysteine degradation pathway, MPST, as a metabolic weakness shared by motile cells across the diverse genetic backgrounds of patient tumors (Cell Death and Disease, 2022).