Marie-Pierre Junier
Sorbonne universities, France
Title: A coupling between a neurotransmitter’s metabolism and epigenetic regulations promotes intra-tumor heterogenity in glioma.
Biography
Biography: Marie-Pierre Junier
Abstract
Cell populations with differing proliferative, stem-like and tumorigenic states co-exist in most tumors and especially malignant gliomas. Whether metabolic variations can drive this heterogeneity by controlling dynamic changes in cell states is unknown. We adressed this question by combining cell biology and neuropathological approaches. Metabolite profiling of human adult glioblastoma stem-like cells upon loss of their tumorigenicity, followed by genetic and pharmaceutical manipulations highlighted a novel signaling module that couples the catabolism of the GABA neurotransmitter and the formation of DNA epigenetic marks. This signaling module was efficient in adult glioblastoma cells with varying molecular profiles, along with cells from pediatric pontine gliomas. Importantly, we verified the relevance of all our findings in the context of the human pathology, using bioinformatics analyzes of patient-derived data at the tissue and single cell level, and immunohistochemical and metabolite analyzes of patients’ tumor samples. These results highlight unexpected levels of heterogeneity among the tumor cells, and support an active participation of metabolic variations in the genesis of tumor heterogeneity.