Team 5: Glial plasticity and neuro-oncology

Growth and resistance to therapy of high-grade glioma are thought to be dictated by glioma stem cells (GSC) that fuel the tumor and contribute to its recurrences. A relevant solution to target GSC is to force their exit from the stem state, and to prevent other tumor cells to acquire stem properties. In this context, we characterized GSC from adult and pediatric high-grade gliomas, and identified compounds toxic for GSC but without effect on human neural stem cells. We uncovered bi-directional interactions of GSC with their microenvironment, and micro-RNAs that trigger loss of their properties. Molecular profiling of GSC forced to exit the stem state revealed unexpected reprogramming in complex networks gathering metabolites, regulators of epigenetics and transcription factors. We currently focus on the functional consequences of these reprogramming on chromatin structure and subsequent GSC behavior, including their interaction with the environment. In parallel, we develop molecular tools to monitor in vivo changes in the cell functional states along tumor development.   Website: http://www.ibps.upmc.fr/fr/Recherche/umr-8246/plasticite-gliale Affiliations: UMR_S UPMC/inserm1130/ CNRS UMR8240 Neurosciences Paris Seine Contact: herve.chneiweiss@inserm.fr

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