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SRP063600
Homo sapiens
12 Downloadable Samples
IlluminaHiSeq2000
Description
Trimethylated histone H3-lysine 4 is primarily distributed in the form of sharp peaks, extending in neuronal chromatin on average only across 500-1500 base pairs mostly in close proximity to annotated transcription start sites. To explore whether H3K4me3 peaks could also extend across much broader domains, we undertook a detailed analysis of broadest domain cell-type specific H3K4me3 peaks in ChIP-seq datasets from sorted neuronal and non-neuronal nuclei in human, non-human primate and mouse prefrontal cortex (PFC), and blood for comparison. Overall design: We collected separately cortical gray (GM) and subcortical white matter (WM) from 6 adult human subjects without neurological disease and extracted total RNA processed by the RNA-Seq approach.
Publication Title
Deciphering H3K4me3 broad domains associated with gene-regulatory networks and conserved epigenomic landscapes in the human brain.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
We have developed efficient protocols for the derivation of mesenchymal precursors from hESCs. While previous protocols were based on mesodermal induction via co-culture of hESCs on OP9 mouse stroma (Barberi et al., PLoS Biology, 2005), our recent work shows the derivation of hESC derived mesenchymal precurors under feeder-free conditions. The data presented here show a large and highly signficant overlap in global gene expression profiles between hESC derived mesenchymal precursors derived under feeder-free conditions with those derived via OP9 co-culure and mesenchymal precurosrs isolated directly from the adult bone marrow.
Publication Title
Derivation of engraftable skeletal myoblasts from human embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Neuronal histone H3-lysine 4 methylation landscapes are defined by sharp peaks at gene promoters and other cis-regulatory sequences, but molecular and cellular phenotypes after neuron-specific deletion of H3K4 methyl-regulators remain largely unexplored. We report that neuronal ablation of the H3K4-specific methyltransferase, Kmt2a/Mixed-lineage leukemia 1 (Mll1), in mouse postnatal forebrain and adult prefrontal cortex (PFC) is associated with increased anxiety and robust cognitive deficits without locomotor dysfunction. In contrast, only mild behavioral phenotypes were observed after ablation of the Mll1 ortholog Kmt2b/Mll2 in PFC. Impaired working memory after Kmt2a/Mll1 ablation in PFC neurons was associated with loss of training-induced transient waves of Arc immediate early gene expression critical for synaptic plasticity. Medial prefrontal layer V pyramidal neurons, a major output relay of the cortex, demonstrated severely impaired synaptic facilitation and temporal summation, two forms of short-term plasticity essential for working memory. Chromatin immunoprecipitation followed by deep sequencing in Mll1-deficient cortical neurons revealed downregulated expression and loss of the transcriptional mark, trimethyl-H3K4, at <50 loci, including the homeodomain transcription factor Meis2. Small RNA-mediated Meis2 knockdown in PFC was associated with working memory defects similar to those elicited by Mll1 deletion. Therefore, mature prefrontal neurons critically depend on maintenance of Mll1-regulated H3K4 methylation at a subset of genes with an essential role in cognition and emotion.
Publication Title
Neuronal Kmt2a/Mll1 histone methyltransferase is essential for prefrontal synaptic plasticity and working memory.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Microarray 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.
Publication Title
Metabolic Reprogramming by MYCN Confers Dependence on the Serine-Glycine-One-Carbon Biosynthetic Pathway.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 42 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The 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.
Publication Title
Proinflammatory caspase-2-mediated macrophage cell death induced by a rough attenuated Brucella suis strain.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
MEIS2 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.
Publication Title
MEIS2 is essential for neuroblastoma cell survival and proliferation by transcriptional control of M-phase progression.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Abnormal 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.
Publication Title
NF-κB2 mutation targets survival, proliferation and differentiation pathways in the pathogenesis of plasma cell tumors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Increased 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.
Publication Title
The histone H3 methyltransferase G9A epigenetically activates the serine-glycine synthesis pathway to sustain cancer cell survival and proliferation.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
HOXC9 directly regulates distinct sets of genes to coordinate diverse cellular processes during neuronal differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Cell 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.
Publication Title
HOXC9 directly regulates distinct sets of genes to coordinate diverse cellular processes during neuronal differentiation.
Sample Metadata Fields
Cell line
View Samples