Purpose: to identify the effects of the Dp1Tyb mutation on the transcriptome of mouse embryonic fibroblasts Overall design: RNAseq libraries were prepared from RNA isolated from mouse embryonic fibroblasts. Libraries were prepared from total RNA using the TruSeq Stranded mRNA Sample Prep Kit (Illumina) by the Advanced Sequencing Facility, The Francis Crick Institute. Libraries were sequenced (100 bases paired end) on the Illumina Hiseq 4000 Please note that this dataset contains ERCC spike ins to normalise the data
Gene expression dysregulation domains are not a specific feature of Down syndrome.
Specimen part, Subject
View SamplesMicroarray gene expression profiling reveals that PHGDH inhibition by NCT-503 activates a metabolic stress response characterized by downregulation of cell cycle genes and induction of stress response genes.
Metabolic Reprogramming by MYCN Confers Dependence on the Serine-Glycine-One-Carbon Biosynthetic Pathway.
Specimen part, Cell line
View SamplesThe macrophage-Brucella interaction is critical for the establishment of a chronic Brucella infection. Smooth virulent B. suis strain 1330 (S1330) prevents macrophage cell death. However, rough attenuated B. suis strain VTRS1 induces strong macrophage cell death. To further investigate the mechanism of VTRS1-induced macrophage cell death, microarrays were used to analyze temporal transcriptional responses of murine macrophage-like J774. A1 cells infected with S1330 or VTRS1.
Proinflammatory caspase-2-mediated macrophage cell death induced by a rough attenuated Brucella suis strain.
Cell line, Treatment
View SamplesMEIS2 has an important role in development and organogenesis, and is implicated in the pathogenesis of human cancer. The molecular basis of MEIS2 action in tumorigenesis is not clear. Here, we show that MEIS2 is highly expressed in human neuroblastoma cell lines and is required for neuroblastoma cell survival and proliferation. Depletion of MEIS2 in neuroblastoma cells leads to M phase arrest and mitotic catastrophe, whereas ectopic expression of MEIS2 markedly enhances neuroblastoma cell proliferation, anchorage-independent growth, and tumorigenicity. Gene expression profiling reveals an essential role of MEIS2 in maintaining the expression of a large number of late cell cycle genes, including those required for DNA replication, G2-M checkpoint control and M phase progression. Importantly, we identify MEIS2 as a transcription activator of the MuvB-BMYB-FOXM1 complex that functions as a master regulator of mitotic gene expression. Further, we show that FOXM1 is a direct target gene of MEIS2 and is required for MEIS2 to upregulate mitotic genes. These findings link a development gene to the control of cell cycle progression and suggest that high MEIS2 expression is a molecular mechanism for high expression of mitotic genes that is commonly observed in cancers of poor prognosis.
MEIS2 is essential for neuroblastoma cell survival and proliferation by transcriptional control of M-phase progression.
Cell line, Treatment
View SamplesAbnormal NF-kB2 activation has been reported in several types of human leukemia and lymphomas although the exact mechanisms and affected pathways are not clear. We have investigated these questions through the use of a unique transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma associated NF-kB2 mutant. Microarray analysis, verified at the RNA and protein level identified new downstream targets and confirmed established regulatory networks. 201 genes were significantly changed, with 126 being upregulated and 75 downregulated. Pathway analysis uncovered both known and unknown interactions between factors important in the development of human B cell lymphomas and multiple myeloma, including cyclins D1 and D2, TRAF1, CD27, BIRC5/survivin, IL-15 and IL-10. Critical roles for STAT3 and TNF receptors are highlighted. Six target genes of STAT3 were identified: cyclins D1and D2, IL-10, survivin, IL-21 and Blimp1. Interfering with STAT3 signaling induced apoptosis in multiple myeloma cell lines. Novel pathways for NF-kB2 are proposed that involve IL-10 and other genes in the differentiation of plasma cells, evasion of apoptosis and proliferation. These pathways were verified with publically available human microarrays. Several treatment strategies based on these findings are discussed.
NF-κB2 mutation targets survival, proliferation and differentiation pathways in the pathogenesis of plasma cell tumors.
Specimen part
View SamplesIncreased activation of the serine-glycine biosynthetic pathway is an integral part of cancer metabolism that drives macromolecule synthesis needed for cell proliferation. Whether this pathway is under epigenetic control is unknown. Here we show that the histone H3 lysine 9 (H3K9) methyltransferase G9A is required for maintaining the pathway enzyme genes in an active state marked by H3K9 monomethylation and for the transcriptional activation of this pathway in response to serine deprivation. G9A inactivation depletes serine and its downstream metabolites, triggering cell death with autophagy in cancer cell lines of different tissue origins. Higher G9A expression, which is observed in various cancers and is associated with greater mortality in cancer patients, increases serine production and enhances the proliferation and tumorigenicity of cancer cells. These findings identify a G9A-dependent epigenetic program in the control of cancer metabolism, providing a rationale for G9A inhibition as a therapeutic strategy for cancer.
The histone H3 methyltransferase G9A epigenetically activates the serine-glycine synthesis pathway to sustain cancer cell survival and proliferation.
Treatment
View SamplesIntranasal (IN) immunization induces different genotype expression in CD8 memory T cells compared to the CD8 memory T cells induced by intramuscular (IM) immunization. We used microarrays to detail the global program of gene expression underlying the differential induction after IN or IM immunization.
Induction of resident memory T cells enhances the efficacy of cancer vaccine.
Specimen part, Treatment
View SamplesThe whole-genome oligonucleotide microarray analysis gives an opportunity for studying the unidentified gene expression background of the idiopathic and H.pylori related gastric erosive alterations. Using microarrays we compared the whole genome gene expression profile of HP+ and HP- gastric erosions and normal adjacent mucosa to explain the possible role and response to HP infection and to get morphology related mRNA expression patterns.
Helicobacter pylori and antrum erosion-specific gene expression patterns: the discriminative role of CXCL13 and VCAM1 transcripts.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
HOXC9 directly regulates distinct sets of genes to coordinate diverse cellular processes during neuronal differentiation.
Specimen part, Cell line
View SamplesCell differentiation is an essential process of normal development by which a stem cell or progenitor cell becomes a post-mitotic, specialized cell with unique morphology and function. Also, it has long been recognized that differentiation is associated with a marked reduction in DNA damage response at the global level. The molecular basis for the coordination between cell cycle exit, acquirement of specialized structure and function, and attenuation of DNA damage response during differentiation is not well understood. We have conducted a genome-wide analysis of the HOXC9-induced neuronal differentiation program in human neuroblastoma cells. Gene expression profiling reveals that HOXC9-induced differentiation is associated with transcriptional regulation of 2,395 genes, which is characterized by global upregulation of neuronal genes and downregulation of cell cycle and DNA repair genes. Remarkably, genome-wide mapping demonstrates that HOXC9 occupies 40% of these genes, including a large number of genes involved in neuronal differentiation, cell cycle progression and DNA damage response. These findings suggest that HOXC9 directly activates and represses the transcription of distinct sets of genes to coordinate the cellular events characteristic of neuronal differentiation.
HOXC9 directly regulates distinct sets of genes to coordinate diverse cellular processes during neuronal differentiation.
Cell line
View Samples