Glioblastoma multiforme is the most common and most aggressive type of primary brain tumor. The brain-infiltrative character of glioblastoma makes complete surgical removal of the tumor impossible and neither radiation nor current chemotherapy provide cure. Recent evidence shows that glioblastoma multiforme consists of heterogeneous cell populations which differ in tumor-forming potential. Enriched tumor-initiating capacity has been linked to poorly differentiated glioblastoma cells sharing features with neural stem cells. Thus, these cells are important targets for new therapeutic strategies.
An RNAi screen identifies TRRAP as a regulator of brain tumor-initiating cell differentiation.
Cell line
View SamplesAdult neurogenesis occurs in mammals and provides a mechanism for continuous neural plasticity in the brain.However, little is known about the molecular mechanisms regulating hippocampal neural progenitor cells (NPCs) and whether their fate can be pharmacologically modulated to improve neural plasticity and regeneration. Here, we report the characterization of a unique small molecule (KHS101) that selectively induces a neuronal differentiation phenotype. Mechanism of action studies revealed a link of KHS101 to cell cycle exit and specific binding to the TACC3 protein, whose knockdown in NPCs recapitulates the KHS101-induced phenotype. Upon systemic administration, KHS101 distributed to the brainandresulted in a significant increase in neuronal differentiation in vivo. Our findings indicate that KHS101 accelerates neuronal differentiation by interaction with TACC3 and may provide a basis for pharmacological intervention.directed at endogenous NPCs.
A small molecule accelerates neuronal differentiation in the adult rat.
Specimen part, Treatment
View SamplesPrimordial germ cells (PGCs), the embryonic precursors of eggs and sperm, are a unique model for identifying and studying regulatory mechanisms in singly migrating cells. From their time of specification to eventual colonization of the gonad, mouse PGCs traverse through and interact with many different cell types, including epithelial cells and mesenchymal tissues. Work in drosophila and zebrafish have identified many genes and signaling pathways involved in PGC migration, but little is known about this process in mammals.
Discrete somatic niches coordinate proliferation and migration of primordial germ cells via Wnt signaling.
Specimen part
View SamplesAscorbate activates CD30 expression and causes widespread specific demethylation of the epigenome of serum free cultured hESC.
Vitamin C promotes widespread yet specific DNA demethylation of the epigenome in human embryonic stem cells.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrated transcriptomic and epigenomic analysis of primary human lung epithelial cell differentiation.
Sex, Specimen part, Time
View SamplesAnalysis of gene expression during differentiation of alveolar epithelial type 2 (AT2) cells into AT1 cells. Timepoints taken at Day 0 (AT2 cell), Days 2, 4, and 6 in culture (differentiating) and Day 8 in culture (AT1-like cells).
Integrated transcriptomic and epigenomic analysis of primary human lung epithelial cell differentiation.
Sex, Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells.
Specimen part, Treatment, Time
View SamplesDNA methylation is a heritable epigenetic modification involved in gene silencing, imprinting, and the suppression of retrotransposons. Global DNA demethylation occurs in the early embryo and the germline and may be mediated by Tet (ten-eleven-translocation) enzymes, which convert 5-methylcytosine (mC) to 5-hydroxymethylcytosine (hmC). Tet enzymes have been extensively studied in mouse embryonic stem (ES) cells, which are generally cultured in the absence of Vitamin C, a potential co-factor for Fe(II) 2-oxoglutarate dioxygenase enzymes like Tets. Here we report that addition of Vitamin C to ES cells promotes Tet activity leading to a rapid and global increase in hmC. This is followed by DNA demethylation of numerous gene promoters and up-regulation of demethylated germline genes. Tet1 binding is enriched near the transcription start site (TSS) of genes affected by Vitamin C treatment. Importantly, Vitamin C, but not other antioxidants, enhances the activity of recombinant human Tet1 in a biochemical assay and the Vitamin C-induced changes in hmC and mC are entirely suppressed in Tet1/2 double knockout (Tet DKO) ES cells. Vitamin C has the strongest effects on regions that gain methylation in cultured ES cells compared to blastocysts and in vivo are methylated only after implantation. In contrast, imprinted regions and intracisternal A-particle (IAP) elements, which are resistant to demethylation in the early embryo, are resistant to Vitamin C-induced DNA demethylation. Collectively, this study establishes that Vitamin C is a direct regulator of Tet activity and DNA methylation fidelity in ES cells.
Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression.
Sex, Age, Specimen part, Race, Subject
View SamplesGene expression profiling of 60 lung adenocarcinoma tumors and their matched histologically normal adjacent lung tissue samples were analyzed using Illumina HumanWG-6 v3.0 expression beadchip. We integrated these data with DNA methylation profiles of the same samples to identify potential DNA methylation regulated genes.
Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression.
Sex, Age, Specimen part, Race, Subject
View Samples