Neuroblastoma (NB) is a neoplasm of the sympathetic nervous system, and is the most common solid tumor of infancy. NBs are very heterogeneous, with a clinical course ranging from spontaneous regression to resistance to all current forms of treatment. High-risk patients need intense chemotherapy, and only 30-40% will be cured. Relapsed or metastatic tumors acquire multi-drug resistance, raising the need for alternative treatments. Owing to the diverse mechanisms that are responsible of NB chemoresistance, we aimed to target epigenetic factors that control multiple pathways to bypass therapy resistance. We found that the SWI/SNF-related, matrix-associated, actin- dependent regulator of chromatin, subfamily a, member 4 (SMARCA4/BRG1) was consistently upregulated in advanced stages of NB, with high BRG1 levels being indicative of poor outcome. Loss-of-function experiments in vitro and in vivo showed that BRG1 is essential for the proliferation of NB cells. Furthermore, whole genome transcriptome analysis revealed that BRG1 controls the expression of key elements of oncogenic pathways such as PI3K/AKT and BCL2, which offers a promising new combination therapy for high-risk NB
BRG1/SMARCA4 is essential for neuroblastoma cell viability through modulation of cell death and survival pathways.
Cell line
View SamplesEffects of IL-4 on CD8 T cells functions are largely unknown. IL-4 induces survival and proliferation of CD8 T cells, but several studies suggest that IL-4 could also affect several functions of CD8 T cells such as cytotoxicity. Our team has shown that IL-4 repress the expression of Ccl5 in vitro.
Negative regulation of NKG2D expression by IL-4 in memory CD8 T cells.
Specimen part, Treatment
View SamplesMacrophages are amongst the major targets of glucocorticoids (GC) as therapeutic anti-inflammatory agents. Here we show that GC treatment of mouse and human macrophages initiates a cascade of induced gene expression including many anti-inflammatory genes. Inducible binding of the glucocorticoid receptor (GR) was detected at candidate enhancers in the vicinity of induced genes in both species and this was strongly associated with canonical GR binding motifs. However, the sets of inducible genes, the candidate enhancers, and the GR motifs within them, were highly-divergent between the two species.
Enhancer Turnover Is Associated with a Divergent Transcriptional Response to Glucocorticoid in Mouse and Human Macrophages.
Sex, Age, Specimen part, Treatment, Time
View SamplesMacrophages are amongst the major targets of glucocorticoids (GC) as therapeutic anti-inflammatory agents. Here we show that GC treatment of mouse and human macrophages initiates a cascade of induced gene expression including many anti-inflammatory genes. Inducible binding of the glucocorticoid receptor (GR) was detected at candidate enhancers in the vicinity of induced genes in both species and this was strongly associated with canonical GR binding motifs. However, the sets of inducible genes, the candidate enhancers, and the GR motifs within them, were highly-divergent between the two species.. The data cast further doubt upon the predictive value of mouse models of inflammatory disease.
Enhancer Turnover Is Associated with a Divergent Transcriptional Response to Glucocorticoid in Mouse and Human Macrophages.
Specimen part, Treatment, Time
View SamplesIn E. coli the phosphate homeostasis is regulated by the Pst system and the two-component system PhoB/R. Pathogens like E. coli O157:H7 are responsible for many outbreaks and can be found and survive in poor inorganic phosphate (Pi) environments.
PhoB activates Escherichia coli O157:H7 virulence factors in response to inorganic phosphate limitation.
No sample metadata fields
View SamplesTibialis anterior muscle was damaged by cardiotoxin injection and macrophage subsets were isolated and analyzed by gene expression analysis.
Highly Dynamic Transcriptional Signature of Distinct Macrophage Subsets during Sterile Inflammation, Resolution, and Tissue Repair.
Time
View SamplesGene expression patterns in the SVZ, 48 h after an ischemic lesion caused by permanent middle cerebral artery occlusion (MCAO)
Astrocytic Calcium Waves Signal Brain Injury to Neural Stem and Progenitor Cells.
Sex, Specimen part
View SamplesLRF, which is encoded by the ZBTB7A gene and formerly known as POKEMON (POK erythroid myeloid ontogenic factor), was originally identified as a PLZF (promyelocytic leukemia zinc finger) homologue interacting with BCL6 (B-cell lymphoma 6). LRF is a transcription factor that is broadly expressed in hematopoietic lineage cells, but its expression is particularly high in erythroblasts and germinal center (GC) B-cells. The goal of this study is to assess the effect of LRF loss on the LT-HSC transcriptome. Nine days after injection of adult mice with polyinosinic polycytidylic acid (pIpc) to activate Cre, total RNAs were isolated from double-sorted LT-HSCs from LRF Flox/+ Mx1-Cre+ and LRF Flox/Flox Mx1-Cre+ mice and processed for microarray analysis.
LRF-mediated Dll4 repression in erythroblasts is necessary for hematopoietic stem cell maintenance.
Age, Specimen part, Time
View SamplesGene expression were identified with or without CD24 gene silencing in Du145 cells.
Intracellular CD24 disrupts the ARF-NPM interaction and enables mutational and viral oncogene-mediated p53 inactivation.
Sex, Specimen part, Cell line
View Samples