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Homo sapiens
12 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Activating mutations of G protein alpha subunits (Ga) occur in 4-5% of all human cancers1 but oncogenic alterations in beta subunits (Gb) have not been defined. Here we demonstrate that recurrent mutations in the Gb proteins GNB1 and GNB2 confer cytokine-independent growth and activate canonical G protein signaling. Multiple mutations in GNB1 affect the protein interface that binds Ga subunits as well as downstream effectors, and disrupt Ga-Gbg interactions. Different mutations in Gb proteins clustered to some extent based on lineage; for example, all eleven GNB1 K57 mutations were in myeloid neoplasms while 6 of 7 GNB1 I80 mutations were in B cell neoplasms. Expression of patient-derived GNB1 alleles in Cdkn2a-deficient bone marrow followed by transplantation resulted in either myeloid or B cell malignancies. In vivo treatment with the dual PI3K/mTOR inhibitor BEZ235 suppressed GNB1-induced signaling and markedly increased survival. In several human tumors, GNB1 mutations co-occurred with oncogenic kinase alterations, including BCR/ABL, JAK2 V617F and BRAF V600K. Co-expression of patient-derived GNB1 alleles with these mutant kinases resulted in inhibitor resistance in each context. Thus, GNB1 and GNB2 mutations confer transformed and resistance phenotypes across a range of human tumors and may be targetable with inhibitors of G protein signaling.
Publication Title
Mutations in G protein β subunits promote transformation and kinase inhibitor resistance.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 64 Downloadable Samples
Affymetrix Clariom S Human array (clariomshuman), Infinium MethylationEPIC
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Epigenomics and transcriptomics of systemic sclerosis CD4+ T cells reveal long-range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci.
Sample Metadata Fields
Sex, Subject
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Epigenomic and transcriptomic analysis of Systemic Sclerosis CD4+ T cells reveals long range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci range dysregulation of key inflammatory pathways mediated by disease-associated
Publication Title
Epigenomics and transcriptomics of systemic sclerosis CD4+ T cells reveal long-range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci.
Sample Metadata Fields
Sex, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The iNSC cells are two clones generated from the same MEF line. Therefore, we conducted one analysis that compared the two clonal lines and a separate analysis that compared iNSC vs. NSC, iNSC vs. MEF, and NSC vs. MEF. Both were single factor ANOVAs, the first compared two
Publication Title
Direct reprogramming of mouse and human fibroblasts into multipotent neural stem cells with a single factor.
Sample Metadata Fields
Specimen part
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
- 34 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
HPV E6 from the genus alpha 'high risk' types such as HPV16 recruit the ubiquitin ligase E6AP to ubiquitinate p53 and target it for proteasome-mediated degradation. This results in the functional inactivation of p53 in HPV16-E6 expressing cells.
Publication Title
Genus beta human papillomavirus E6 proteins vary in their effects on the transactivation of p53 target genes.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Schizosaccharomyces pombe
- 12 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
In addition to its well-know function in chromosome segregation, increasing evidence implicates cohesin in the control of gene expression. It has been previously reported that inactivation of the cohesin loader Mis4 in G1-arrested cells leads to the dissociation of cohesin from chromatin. We exploited this experimental situation to ask whether this loss of cohesin would affect gene expression on a genome-wide scale.
Publication Title
Role for cohesin in the formation of a heterochromatic domain at fission yeast subtelomeres.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 87 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Analysis of gene expression over serial 150um sections of a single gestational week 14.5 human neocortical specimen. The hypothesis tested with this dataset was that a transcriptional signature of radial glia (neural stem cells) could be isolated via unsupervised gene coexpression analysis due to variation in the abundance of this cell type from section to section. This dataset is the first of its kind generated using this method (Gene Coexpression Analysis of Serial Sections, or GCASS).
Publication Title
Radial glia require PDGFD-PDGFRβ signalling in human but not mouse neocortex.
Sample Metadata Fields
Age, Specimen part
View Samples
GSE33728- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Systematic classification of melanoma cells by phenotype-specific gene expression mapping.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 23 Downloadable Samples
NextSeq 500
Description
Histological resolution of the murine pancreas occurs within one week after injury. Whether histological resolution constitutes pancreatic recovery at a molecular level is not known. We performed RNA-sequencing on the recovering pancreas to determine the transcriptomic profile within the histologically recovered pancreas. We show that although there is histological resolution one week after injury in mice, compared to baseline (non-injured pancreas), there are still numerous differentially expressed genes (DEGs) at one and even two weeks after injury. Overall, the findings suggest the actual recovery takes longer than initially thought given the differential transcriptomic profile in the pancreas two weeks after injury compared to the baseline pancreas. There is also the possibility of a novel emerging pancreatic transcriptome upon recovery. Overall design: Acute pancreatitis was induced by caerulein hyperstimulation in both male and female C57BL/6 mice. Total RNA was extracted from the head of the murine pancreas in mice at baseline (non-injured; n=8), day 7 (post-injury; n=8), and day 14 (post-injury; n=7). Total stranded RNA libraries (ribo-depleted) were generated and sequenced on the Illumina NextSeq 500 NGS platform. RNA-seq data was analyzed for differentially expressed genes between baseline and day 7 and between baseline and day 14.
Publication Title
Pancreatic gene expression during recovery after pancreatitis reveals unique transcriptome profiles.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples