CNS-delivery of Interleukin 4 (IL-4) - via a lentiviral-mediated gene therapy strategy - skews microglia to proliferate, inducing these cells to adopt the phenotype of slowly proliferating cells. Transcriptome analysis revealed that IL-4-treated microglia express a broad number of genes normally encoded by embryonic microglia. Overall design: RNAseq analysis of sorted microglia from mice receiving IL-4 gene therapy
Interleukin 4 modulates microglia homeostasis and attenuates the early slowly progressive phase of amyotrophic lateral sclerosis.
Specimen part, Cell line, Subject
View SamplesFour Wnt-dependent and four Wnt-independent GSC cultures were grown in stem cell media and RNA expression between the two subsets evaluated Overall design: Four biological replicates each of Wnt-dependent and Wnt-independent GSC cultures
Wnt and Notch signaling govern self-renewal and differentiation in a subset of human glioblastoma stem cells.
Specimen part, Cell line, Subject
View SamplesPrimary glioblastoma (GBM) cultures vary with respect to differentiation competency. We sought to identify putative transcription factors necessary for the differentiation of GBM cultures. In this dataset, we include expression data obtained from 2 human-fetal neural stem cell (HF-NS) cultures and 2 GBM stem cell (GSC) cultures. We assessed changes in gene expression from 3 timepoints during an in vitro differentiation protocol.
ASCL1 Reorganizes Chromatin to Direct Neuronal Fate and Suppress Tumorigenicity of Glioblastoma Stem Cells.
Specimen part, Time
View SamplesMutations in the histone 3 variant H3.3 have been identified in one-third of pediatric glioblastomas (GBMs), but not in adult tumors. Here we show that H3.3 is a dynamic determinant of functional properties in adult GBM. H3.3 is repressed by mixed lineage leukemia 5 (MLL5) in self-renewing GBM cells. MLL5 is a global epigenetic repressor that orchestrates reorganization of chromatin structure by punctuating chromosomes with foci of compacted chromatin, favoring tumorigenic and self-renewing properties. Conversely, H3.3 antagonizes self-renewal and promotes differentiation. We exploited these epigenetic states to rationally identify two small molecules that effectively curb cancer stem cell properties in a preclinical model. Our work uncovers a role for MLL5 and H3.3 in maintaining self-renewal hierarchies in adult GBM.
MLL5 Orchestrates a Cancer Self-Renewal State by Repressing the Histone Variant H3.3 and Globally Reorganizing Chromatin.
Specimen part, Time
View SamplesThe small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains that contribute to the viral life cycle, including the DNA binding and helicase domains. In addition, the LT the C-terminal region is required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells and identified interacting cellular proteins and performed expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes.
Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The effects of EBV transformation on gene expression levels and methylation profiles.
Sex, Specimen part, Subject
View SamplesEpstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) provide a conveniently accessible and renewable resource for functional studies in humans. The ability to accumulate multidimensional data pertaining to the same individual cell lines, from complete genomic sequences to detailed gene regulatory profiles, further enhances the utility of LCLs as a model system. A lingering concern, however, is that the changes associated with EBV transformation of LCLs reduce the usefulness of LCLs as a surrogate model for primary tissues. To evaluate the validity of this concern, we compared global gene expression profiles between CD20+ primary B cells and CD3+ primary T cells sampled from six individuals. Six independent replicates of transformed LCLs were derived from each sample.
The effects of EBV transformation on gene expression levels and methylation profiles.
Sex, Specimen part, Subject
View SamplesOverexpression of a grapevine C-repeat binding factor (CBF) gene, VvCBF4 in cv. Freedom was found to improve freezing survival in non-cold-acclimated vines.
The Vitis vinifera C-repeat binding protein 4 (VvCBF4) transcriptional factor enhances freezing tolerance in wine grape.
Specimen part
View SamplesTGF is one of most intensively studied regulators of extracellular matrix formation, and has been implicated in the development of pulmonary fibrosis in different models. However, little is know about the role of miRNAs in TGF mediated fibrogenic gene regulation. By using miRNA qRT-PCR array, we have identified miRNAs whose expression are regulated by TGF in IMR-90 cells. Among those down-regulated miRNAs are miR-29 family members. Knockdown miR-29 in IMR-90 cells results in up-regulation of a large number of extracellular matrix and fibrogenic genes including family members of collagen, laminin, integrin, ADAM and MMP, many of them are predicted or confirmed miR-29 targets. Hierarchichal clustering analysis of mRNA array data revealed that many extracellular matrix and fibrogenic genes up-regulated by TGF in IMR-90 cells, are also up-regulated in miR-29 KD cells. Moreover, the similar set of extracellular matrix and fibrogenic genes is also significantly up-regulated in bleomycin treated mouse lungs. Together, our data strongly suggest that downstream of the TGF, miR-29 is a master modulator of genes involved in extracellular matrix formation and might play a significant role in pulmonary fibrosis.
miR-29 is a major regulator of genes associated with pulmonary fibrosis.
Specimen part, Cell line
View SamplesIn the present study, we have investigated the effect of CpG Oligodeoxynucleotides (CpG-ODN) on the outcome of Plasmodium infection of the mosquito vectors Anopheles stephensi and Anopheles gambiae and on the modulation of mosquito immunity to Plasmodium. Anopheles mosquitoes inoculated with CpG-ODN showed significant reduction of Plasmodium infection rate and intensity. Microarrays were used to profile transcription of fat-body from CpG-ODN-treated mosquitoes. Mosquitoes were dissected 18h after ODN inoculation (immediately before feeding). Batches of 20 to 30 fat bodies (abdomen without midgut, ovaries and malpighian tubule]) were dissected in cold DEPC-treated phosphate-buffered saline (PBS) and processed for RNA preparation. Mosquitoes treated with CpG-ODNs are less susceptible to Plasmodium infection. Transcription profile of fat body indicates that protection was associated with coagulation/wound healing, while melanization appears to be depressed.
CpG-containing oligodeoxynucleotides increases resistance of Anopheles mosquitoes to Plasmodium infection.
Sex, Specimen part, Treatment
View Samples