EXPRESSION AND INITIAL CHARACTERIZATION OF THE CELL FATE TRANSCRIPTION FACTOR PRDM1 IN ADULT NEURAL PROGENITORS AND GLIOBLASTOMA MULTIFORME

PRDM1 is a master transcriptional regulator in multiple cell lineages and it is required for the development of many species. However the reason and the mechanisms underlying its pleiotropic functions remain largely unknown as the full array of tissues and target genes controlled by PRDM1. Our results indicate a completely unexplored field where to study PRDM1 regulatory network that is the brain and its most aggressive cancer, the Glioblastoma multiforme (GBM). We identified that PRDM1 is expressed in adult neural progenitor cells and that it correlates with the maintenance of cellular multipotency possibly by interfering with pro-differentiation pathways (e.g. HIF1α signaling). We generated the first genome wide profile of PRDM1 binding in mammalian cells, expanding the pool of known direct target genes and providing a new solid ground for mechanistical studies that suggest a role for PRDM1 in stable and heritable gene silencing during differentiation. Finally we found that PRDM1 expression associates with a specific subtype of human GBM called mesenchymal and that it is highly expressed in GBM cancer derived stem cells. Consequently we are now exploiting the functional relevance of PRDM1 in a spontaneous mouse model of GBM related to the human pathology. Taken together our data add further to the already established role of PRDM1 as a cell fate regulator identifying that PRDM1 is involved in normal and aberrant mammalian neurogenesis. We also provided a consistent dataset to functionally and mechanistically characterize PRDM1 regulatory network.