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Directed neuronal differentiation of stem-like glioma initiating cells

16th national competition for scientific and technical research

Rare diseases

Senior Researcher : Núria de la Iglesia Zaragoza

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Research Centre or Institution : Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS). Barcelona.


Gliomas are one of the most aggressive tumours in humans. They have a subpopulation of tumoral cells that present "stem-like" properties, such as auto-renovation, pluripotentiality and the ability to recapitulate the original tumour through transplant into a healthy host. These cells, known as Glioma Initiating Cells (GIC) share characteristics with normal neural stem cells, which are able to generate the three main cell types of the central nervous system: neurons, astrocytes and oligodendrocytes. This finding has opened the doors to new therapies specifically targeting GIC, given that these cells may be responsible for the recurrence of the tumour after conventional anti-cancer treatments. These newly emerging treatments include pro-differentiating therapies, which stimulate the differentiation of stem-like GIC, thereby depriving them of their tumorigenic properties. This study aims to apply a differentiating pro-neuronal therapy to gliomas, while taking it a step further. It proposes not only to promote the neuronal differentiation of GIC to induce a state of post-mitotic differentiation, but also to sensitize these glioma initiating cells to spontaneous apoptosis, taking advantage of the mutational profile of the tumour itself.

Throughout 2012, a collection of GIC cell-lines was obtained, and these have been classified according to their expression of Ink4a/Arf tumoral suppressors. This classification makes it possible to predict which type of GIC will respond better to pro-neuronal therapy. In turn, lentivirus was obtained to generate GIC lines that inducibly express pro-neural genes (Ngn1, NeuroD1, etc.). The first experiments with neuronal differentiation induction in culture are now under way.

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