Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:Although a growing body of evidence indicates that the phenotypic plasticity exhibited by glioblastoma cells plays a central role in tumor development and post-therapy recurrence, the master drivers of their aggressiveness remain elusive. Here we mapped the changes in the transcriptionally permissive (H3K4me3) and repressive (H3K27me3) epigenetic histone marks accompanying the repression of glioblastoma stem cells (GSC) tumorigenicity. Genes with changing marks delineated a network of transcription factors related to cancerous behavior, stem state, and neural development, which highlighted a previously unsuspected association between repression of ARNT2 and loss of cell tumorigenicity. Immunohistochemistry confirmed ARNT2 expression in cell sub-populations of patients’ glioblastoma. Its transcriptional repression was consistently found in non-tumorigenic glioblastoma cells, compared to tumorigenic cells. Moreover, ARNT2 expression correlated with a stem signature at both the tissue level within the tumor core and at the single cell level in the patients’ tumors. ARNT2 knockdown decreased expression of the transcription factors SOX9, POU3F2 and OLIG2 known promoters of glioblastoma cell tumorigenicity, and repressed GSC tumorigenic properties in vivo. Our results unveil ARNT2 as a master gene of the glioblastoma tumorigenic cell signature, located at a node of the transcription factor network controlling glioblastoma cell aggressiveness.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
Project description:The subset of GBM patient samples gives rise to adherent cultures even in sphere culture conditions. Most samples in this subset are tumorigenic and exhibit a hybrid expression profile when tested with the marker panel. Cultures from these samples have a predominantly mesenchymal character based on substrate adherence, morphology, differentiation potential and gene expression. Total RNA isolated from glioblastoma stem cells (GSC) cultured as spheres was compared to that from adherent GSCs cultured in sphere culture conditions that exhibited both GSC and mesenchymal properties.