Background: Insulin's effect on protein synthesis (translation of transcripts) and post-translational modifications, especially those involving reversible modifications such as phosphorylation of various signaling proteins, are extensively studied. On the other hand, insulin's effect on the transcription of genes, especially of transcriptional temporal patterns, is not well investigated in the literature.
Function-based discovery of significant transcriptional temporal patterns in insulin stimulated muscle cells.
Specimen part, Cell line, Treatment
View SamplesDown syndrome (DS) results from trisomy of chromosome 21 (HSA21). Some DS phenotypes may be directly or indirectly related to the increased expression of specific HSA21 genes, in particular those encoding transcription factors. The HSA21 encoded Single-minded 2 (SIM2) transcription factor has key neurological functions and is a good candidate to be involved in the cognitive impairment of DS. ChIP-sequencing was used to map SIM2 binding in mouse embryonic stem cells and has revealed 1229 high-confidence SIM2-binding sites. Analysis of the SIM2 target genes confirmed the importance of SIM2 in developmental and neuronal processes and indicated that SIM2 may be a master transcription regulator. Indeed, SIM2 DNA binding sites share sequence specificity and overlapping domains of occupancy with master transcription factors such as SOX2, OCT4, NANOG or KLF4. The association between SIM2 and these pioneer factors is supported by the finding that SIM2 can be co-immunoprecipitated with SOX2, OCT4, NANOG or KLF4. Furthermore, the binding of SIM2 marks a particular sub-category of enhancers known as super-enhancers. These regions are characterized by typical DNA modifications and Mediator co-occupancy (MED1 and MED12). Altogether, we provide evidence that SIM2 binds a specific set of enhancer elements thus explaining how SIM2 can regulate its gene network in DS neuronal features. Overall design: RNA-Seq analysis in Sim2 expressing cells (3 replicates A6, B8, C4) and EB3 control cells (3 replicates)
HSA21 Single-Minded 2 (Sim2) Binding Sites Co-Localize with Super-Enhancers and Pioneer Transcription Factors in Pluripotent Mouse ES Cells.
No sample metadata fields
View SamplesThe HSA21-mES Cell Bank includes, in triplicate clones, thirty-two murine orthologs of HSA21 genes, which can be overexpressed in an inducible manner using the Tet-off system integrated in the Rosa26 locus.
A mouse embryonic stem cell bank for inducible overexpression of human chromosome 21 genes.
Specimen part
View SamplesThe goal of our study was to molecularly dissect mesothelioma tumor pathways by mean of microarray technologies in order to identify new tumor biomarkers, that could be used as early diagnostic markers and possibly as specific molecular therapeutic targets. We performed Affymetrix U133A plus 2.0 microarray analysis comparing 9 human pleural mesotheliomas with 4 normal pleural specimen. Stringent statistical feature selection detected a set of differentially expressed genes that were further evaluated to identify potential biomarkers to be used in early diagnostics. Selected genes were confirmed by RT-PCR. As reported by other mesothelioma profiling studies, most of genes are involved in G2/M transition. Our list contains several genes previously described as prognostic classifier. Furthermore, we found novel genes never associated before to mesothelioma and could be involved in tumor progression. Notable, the identification of MMP-14, a member of matrix metalloproteinase family. This molecule has been described as a new disease marker and could be used as biomarker also for mesothelioma early diagnosis and prognosis and that can be viewed as new and effective therapeutic target to test.
Global gene expression profiling of human pleural mesotheliomas: identification of matrix metalloproteinase 14 (MMP-14) as potential tumour target.
No sample metadata fields
View SamplesSamples 1-4 report RNA-seq transcriptome profiling of the L-Proline- (L-Pro) and bFgf/ActivinA- (F/A) derived mCherry+/eGFP+ (yellow) ESC population, using the Illumina HiSeq platform. Whole-genome expression revealed that more than 1000 genes were significantly deregulated in L-Pro- and F/A-induced cells compared to control (mCherry+/eGFP- red cells) and the two population shared up to 75% of deregulated genes with the same deregulation trend. Specifically, the pluripotency-associated genes were downregulated either at similar level (Nanog, Klf2, Klf4 and Gbx2) or at lower levels (up to 10 times) (Dppa 2, 3, 4, 5a, Rex1, Esrrb) in F/A- compared to L-Pro-treated cells. Interestingly, mesendodermal-related genes (e.g. Brachyury, Cer1, Dkk1, Eomes, Foxa2, and Sox17) were induced in both conditions but at significant higher levels in F/A- compared to L-Pro-treated cells. The transcriptome analysis of mCherry+/eGFP+ (yellow) cells supported the idea that L-Pro mimics F/A in inducing a naïve to primed transition, and suggested that it exerted a milder (weaker) effect. Samples 5-14 report RNA-seq transcriptome profiling of the mir-290_mCherry/mir-302_eGFP dual reporter ESCs (DRESCs) bulk culture, grown in FBS/LIF ± VitaminC (VitC) and L-Proline (L-Pro) and compared them to the standard naive/2i and primed/bFgf/ActivinA-EpiSCs (F/A), using the Illumina HiSeq platform. Whole-genome expression identified around 7900 deregulated genes in the different conditions, (fold change=2 and pvalue<0.05). Principal component analysis (PCA) placed VitC between 2i and untreated control, and L-Pro between control and F/A. Accordingly, a set of pluripotency-associated genes was expressed at higher level in 2i and VitC conditions, while downregulated in L-Pro and F/A, compared to control. Conversely, priming markers were downregulated in 2i and VitC and upregulated in L-Pro and F/A compared to control The transcriptome analysis supported that VitC- and L-Pro captured alternative pluripotency states that can be likely placed between naïve/2i and primed/F/A states. Overall design: RNA-seq profiling of ESCs grown in FBS/LIF ± VitC, 2i, L-Pro or F/A, using the Illumina HiSeq platform
Vitamin C and l-Proline Antagonistic Effects Capture Alternative States in the Pluripotency Continuum.
Cell line, Subject
View SamplesPeriostin participates in different processes involved in connective tissue homeostasis. It is also involved in repairment of damaged tissues. We used the osteoblast murine cell line MC3T3-E1 cell line to show how overexpresion of periostin is able to increase their adhesion properties while diminishing their migration capacity. By differential gene expression we evaluated putative targets involved in those cellular properties.
Role of Periostin in Adhesion and Migration of Bone Remodeling Cells.
Specimen part, Cell line
View SamplesWe hypothesized that broad-scale expression profiling would provide insight into the regulatory pathways that control gene expression in response to stress, and potentially identify novel heat-responsive genes. HEp2 cells were heated at 37 to 43 C for 60 min to gauge the heat shock response, using as a proxy inducible HSP-70 quantified by western blot analysis. Based on these results, microarray experiments were conducted at 37, 40, 41, 42 and 43C (3 replicates/temperature x 5 groups = 15 U95Aver2 GeneChips). Using linear modeling, we compared the sets of microarrays at 40, 41, 42 and 43C with the 37C baseline temperature and took the union of the genes exhibiting differential gene expression signal to create two sets of heat shock response genes, each set reflecting either increased or decreased RNA abundance. Leveraging human and mouse orthologous alignments, we used the two lists of co-expressed genes to predict transcription factor binding sites in silico, including those for heat shock factor 1 (HSF1) and heat shock factor 2 (HSF2) transcription factors. We discovered HSF1 and HSF2 binding sites in 15 genes not previously associated with the heat shock response. We conclude that microarray experiments coupled with upstream promoter analysis can be used to identify novel genes that respond to heat shock. Additional experiments are required to validate these putative heat shock proteins and facilitate a deeper understanding of the mechanisms involved during the stress response.
Transcriptional profiles of human epithelial cells in response to heat: computational evidence for novel heat shock proteins.
No sample metadata fields
View SamplesGlioblastoma multiforme (GBM) is a highly malignant primary central nervous neoplasm characterized by tumor cell invasion, robust angiogenesis, and a mean survival of 15 months. Human cytomegalovirus (HCMV) infection is present in > 90% of GBMs, although the role the virus plays in GBM pathogenesis is unclear. We report here that a majority of human GBM tumors express HCMV pp71, which has previously been found to promote cell cycle progression and viral replication, and that pp71 is expressed preferentially within the CD133+ cancer stem cell-like subpopulation. Overexpression of pp71 in adult neural precursor cells (NPCs) resulted in a dramatic induction of stem cell factor (SCF) gene expression, which has been identified as an important pro-angiogenic factor in GBM.
Cytomegalovirus pp71 protein is expressed in human glioblastoma and promotes pro-angiogenic signaling by activation of stem cell factor.
Cell line
View SamplesDeep sequencing of splenic RbLo TEM and RbHi TN cells 72 hours following anti-CD3 stimulation. Overall design: mRNA was collected from snap-frozen cells at 72 hours post stimulation.
CD45Rb-low effector T cells require IL-4 to induce IL-10 in FoxP3 Tregs and to protect mice from inflammation.
Specimen part, Cell line, Subject
View SamplesRegulation of genes in shoots and roots and Arabidopsis in response to Zn-deficiency in wild-type and hma2 hma4 mutants plants
Systemic Upregulation of MTP2- and HMA2-Mediated Zn Partitioning to the Shoot Supplements Local Zn Deficiency Responses.
Age, Specimen part
View Samples