We report RNAseq data from subsequent passages of five organoid cultures. Overall design: RNA extracted from subsequent PDO passages was subjected to RNAseq.
Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.
Disease, Subject
View SamplesEffect of LPS, CpG, dexamethasone, Pam3Cys, poly I:C, zymosan, Schistosoma mansoni eggs, Schistosoma mansoni shistosomula, Listeria monocytogenes, Leishmania mexicana amastigotes and Leishmania mexicana promastigotes on dendritic cell gene transcription
Gene expression profiles identify inflammatory signatures in dendritic cells.
Sex, Specimen part, Cell line, Treatment, Compound, Time
View SamplesThe regulation of necrotic death and its relevance in anti-cancer therapy are largely unknown. Here we have investigated the pro-apoptotic and pro-necrotic activities of two ubiquitin-proteasome system inhibitors (UPSIs): bortezomib and G5. The present study points out that the glioblastoma cell lines U87MG and T98G are useful models to study the susceptibility to apoptosis and necrosis in response to UPSIs. U87MG cells are resistant to apoptosis induced by bortezomib and G5 but susceptible to necrosis induced by G5. On the opposite T98G cells are susceptible to apoptosis induced by both inhibitors but show some resistance to G5-induced necrosis. By comparing the transcriptional profiles of the two cell lines, we have found that the resistance to G5-induced necrosis could arise from differences in glutathione synthesis/utilization and in the microenvironment. In particular collagen IV, which is highly expressed in T98G cells, and fibronectin, whose adhesive function is counteracted by tenascin-C in U87MG cells, can restrain the necrotic response to G5. Collectively, our results provide an initial characterization of the molecular signals governing cell death by necrosis in glioblastoma cell lines.
Characterization of caspase-dependent and caspase-independent deaths in glioblastoma cells treated with inhibitors of the ubiquitin-proteasome system.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells.
Specimen part, Cell line, Treatment
View SamplesThe deposition of unconjugated bilirubin (UCB) in selected regions of the brain results in irreversible neuronal damage, or Bilirubin Encephalopathy (BE). Although UCB impairs a large number of cellular functions, the basic mechanisms of neurotoxicity have not yet been fully clarified. While cells can accumulate UCB by passive diffusion, cell protection may involve multiple mechanisms including the extrusion of the pigment as well as pro-survival homeostatic responses that are still unknown. The effects of UCB treatment to SH-SY5Y neuroblastoma cell line were examined by high density oligonucleotide microarrays. 230 genes were induced after 24 hours. A Gene Ontology (GO) analysis showed that a large group of UCB-induced genes were components of the ER stress response. Independent experimental validation of molecular events crucial for the ER stress response is presented. The results show that UCB exposure induces ER stress response as major intracellular homeostatic response in neuroblastoma cells in vitro. Our finding may provide valuable information for new therapeutic strategies in the treatment of BE.
A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells.
Specimen part
View SamplesThe deposition of unconjugated bilirubin (UCB) in selected regions of the brain results in irreversible neuronal damage, or Bilirubin Encephalopathy (BE). Although UCB impairs a large number of cellular functions, the basic mechanisms of neurotoxicity have not yet been fully clarified. While cells can accumulate UCB by passive diffusion, cell protection may involve multiple mechanisms including the extrusion of the pigment as well as pro-survival homeostatic responses that are still unknown. The effects of UCB treatment to SH-SY5Y neuroblastoma cell line were examined by high-density oligonucleotide microarrays. 230 genes were induced after 24 hours. A Gene Ontology (GO) analysis showed that a large group of UCB-induced genes were components of the ER stress response. Independent experimental validation of molecular events crucial for the ER stress response is presented. The results show that UCB exposure induces the ER stress response as a major intracellular homeostatic response in neuroblastoma cells in vitro. Our finding may provide valuable information for new therapeutic strategies in the treatment of BE.
A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells.
Specimen part, Cell line, Treatment
View SamplesThe deposition of unconjugated bilirubin (UCB) in selected regions of the brain results in irreversible neuronal damage, or Bilirubin Encephalopathy (BE). Although UCB impairs a large number of cellular functions, the basic mechanisms of neurotoxicity have not yet been fully clarified. While cells can accumulate UCB by passive diffusion, cell protection may involve multiple mechanisms including the extrusion of the pigment as well as pro-survival homeostatic responses that are still unknown. The effects of UCB treatment to SH-SY5Y neuroblastoma cell line were examined by high-density oligonucleotide microarrays. 230 genes were induced after 24 hours. A Gene Ontology (GO) analysis showed that a large group of UCB-induced genes were components of the ER stress response. Independent experimental validation of molecular events crucial for the ER stress response is presented. The results show that UCB exposure induces the ER stress response as a major intracellular homeostatic response in neuroblastoma cells in vitro. Our finding may provide valuable information for new therapeutic strategies in the treatment of BE.
A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells.
Specimen part, Cell line, Treatment
View SamplesDJ-1 is an atypical peroxiredoxin-like peroxidase that may act as a redox-dependent chaperone and a regulator of transcription. To explore DJ-1-mediated transcriptional control in Parkinsons disease (PD), we generated human neuroblastoma cells with inducible knock-down of DJ-1 expression. We then used functional genomic techniques to identify novel pathways dysregulated by loss of DJ-1 function. Using microarray gene expression profiling, we found that DJ-1 silencing alters the expression of 26 genes, with 10 down-regulated and 16 up-regulated transcripts. Among the down-regulated genes we found Ret, tyrosine kinase receptor for the neurotrophic factor GDNF. Taking advantage of Ingenuity Pathways Analysis, we identified hypoxia inducible factor 1 alpha (Hif1a) as a possible mediator of the interplay between DJ-1 and Ret. We show that Hif1a is stabilized in the absence of DJ-1, and that loss of DJ-1 generates hypoxia and accumulation of free radical species (ROS). Overexpression of wt DJ-1, but not of C106A and L166P mutants deficient in ROS scavenger activity, rescues Ret expression in neuroblastoma cells. These findings reveal novel players in PD pathogenesis and provide evidence for additional pathways involved in DJ-1-mediated neurodegeneration.
Parkinson disease-associated DJ-1 is required for the expression of the glial cell line-derived neurotrophic factor receptor RET in human neuroblastoma cells.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The role of histone demethylase KDM4B in Myc signaling in neuroblastoma.
Cell line, Treatment
View SamplesEpigenetic alterations appear to modulate Myc signaling. We investigated the role of the histone demethylase JMJD2B in Myc-mediated neuroblastoma pathogenesis. We demonstrate that Myc physically interacts with and recruits this epigenetic modifier, which removes repressive H3K9 methyl marks from Myc-target genes. JMJD2B regulates neuroblastoma proliferation and, together with MYCN amplification, identifies a subgroup of poor prognosis patients. We identify a novel histone demethylase inhibitor, ciclopirox, which targets JMJD2B and, consequently, Myc signaling, thereby inhibiting neuroblastoma proliferation and inducing differentiation. In xenograft studies, genetic and pharmacologic inhibition of JMJD2B resulted in significant tumor growth restriction. Our findings provide insight into epigenetic regulation of Myc via histone methylation and proof-of-concept for pharmacologic inhibition of histone demethylases to target Myc signaling in cancer.
The role of histone demethylase KDM4B in Myc signaling in neuroblastoma.
Cell line, Treatment
View Samples