This dataset is part of the manuscript titled "The metabolic regulator ERRalpha, a downstream target of HER2/IGF1, as a therapeutic target in breast cancer" (in review). The expression data obtained in human mammary epithelial cells were used to generate a list of ERRalpha-regulated genes that was later refined in clinical breast cancer datasets to generate a clinically relevant signature of ERalpha activity (referred to as Cluster 3 signature). Using this signature of the estrogen-related receptor alpha (ERRa) to profile more than eight-hundred breast tumors, we found that patients with tumors exhibiting higher ERRa activity were predicted to have shorter disease free survival. Further, the ability of an ERRa antagonist, XCT790, to inhibit breast cancer cell proliferation correlates with the cells intrinsic ERRa activity. These findings highlight the potential of using the ERRa signature and antagonists in targeted therapy for breast cancer. Using a chemical genomic approach we determined that activation of the HER2/IGF1 signaling pathways upregulates the expression of PGC-1b, an obligate cofactor for ERRa activity. Knockdown of PGC-1b in HER2 positive breast cancer cells impaired ERRa signaling and reduced cell proliferation, implicating a functional role of PGC1b/ERRa in the pathogenesis HER2 positive breast cancer.
The metabolic regulator ERRα, a downstream target of HER2/IGF-1R, as a therapeutic target in breast cancer.
Specimen part
View SamplesMedulloblastoma is a malignant brain tumor that occurs predominantly in children. Current risk stratification based on the clinical parameters is inadequate for accurate prognostication. In order to get a better understanding of medulloblastoma biology, miRNA profiling of medulloblastomas was carried out in parallel with the expression profiling of protein- coding genes.
Distinctive microRNA signature of medulloblastomas associated with the WNT signaling pathway.
Sex
View SamplesProfiling of the transcriptome of FITChigh/FSCdim and FITCdim/FSChigh sub-populations. Three biological replicates were profiled for each cell type. Overall design: Profiling of the transcriptome of FITChigh/FSCdim and FITCdim/FSChigh sub-populations. Three biological replicates were profiled for each cell type.
An autofluorescence-based method for the isolation of highly purified ventricular cardiomyocytes.
Specimen part, Cell line, Subject
View SamplesTGF-beta3 produced by developing Th17 cells induces highly pathogenic T cells that are functionally and molecularly distinct from TGF-beta1-induced Th17 cells. The microarray data represent a distinct molecular signature for pathogenic versus non-pathogenic Th17 cells.
Induction and molecular signature of pathogenic TH17 cells.
Sex, Specimen part
View SamplesMethylation at 5-cytosine (5-mC) is a fundamental epigenetic DNA modification associated recently with cardiac disease. In contrast, the role of 5-hydroxymethylcytosine (5-hmC) – 5-mC's oxidation product – is unknown in the context of the heart. Here, we assess the hydroxymethylome in embryonic, neonatal, adult and hypertrophic mouse cardiomyocytes, showing that dynamic modulation of hydroxymethylated DNA is associated with specific transcriptional networks during heart development and failure. DNA hydroxymethylation marks gene bodies of highly expressed genes and distal regulatory regions with enhanced activity. Pathological hypertrophy is characterized by a partial shift towards a fetal-like distribution pattern. We further demonstrate a regulatory function of TET2 and provide evidence that the expression of key cardiac genes, such as Myh7 is modulated by TET2-mediated 5-hmC deposition on the gene body and at enhancers in cardiac cells. We thus provide the first genome-wide analysis of 5-hmC in the cardiomyocyte, and establish the role of this epigenetic modification in heart development and disease Overall design: Profiling of the transcriptome of embryonic, neonatal, adult, 1 week hypertrophic cardiomyocytes, sh-control and sh-TET2 cardiomyocytes. Two biological replicates were profiled for each cell type.
DNA hydroxymethylation controls cardiomyocyte gene expression in development and hypertrophy.
Specimen part, Cell line, Subject
View SamplesPeriodontitis affects 47.1% of adult population in the U.S. Porphyromonas gingivalis is an opportunistic oral pathogen that colonizes the oral mucosa, invades myeloid dendritic cells and accesses the bloodstream, brain, placenta and other organs in human with periodontitis. Periodontitis also sustains a chronic long-term pro-inflammatory immune disorder, potentially contributing to other systemic conditions such as cardiovascular disease, type 2 diabetes mellitus, adverse pregnancy outcomes, and osteoporosis. However, the role of P. gingivalis minor and major fimbriae in DC-SIGN-TLR2 crosstalk during traverses from oral mucosa to these distant sites and its influence on survival of P. gingivalis within DCs and its immune-mechanism involve at molecular/transcriptome level has not been examined. In this study to address the role of fimbriae we utilized defined bacterial mutants that solely express minor fimbriae (Mfa1+Pg), major fimbriae (FimA+Pg) or are deficient in both fimbriae (MFB) and compared with un-infected control. P. gingivalis strains were maintained anaerobically (10% H2, 10% CO2, and 80% N2) in a Forma Scientific anaerobic system glove box model 1025/1029 at 37°C in Difco anaerobe broth MIC. Mutant strains were maintained using erythromycin (5 µg/ml) for mutant Mfa1+Pg, tetracycline (2 µg/ml) for mutant FimA+Pg and both erythromycin and tetracycline for double fimbriae mutant MFB. Bacterial suspensions were washed five times in PBS and re-suspended for spectrophotometer reading at OD 660 nm of 0.11, which previously determined to be equal to 5 x 107 CFU. For bacterial CFSE staining, the suspension were washed (3 times) and re-suspended in 5 µM of CFSE in PBS. The bacteria were incubated for 30 min at 37°C in the dark. MoDCs were pulsed with Pg381, Mfa1+Pg, FimA+Pg and MFB at 10 MOI and incubated with the MoDCs for 12 hours and each experimental condition was performed in triplicate. Overall design: To facilitate our understanding on host immunity and defense mechanism of this pathogen, here we used the Illumina High-throughput RNA-seq transcriptome profiling to investigate the myeloid dendritic cells response to oral Amphibiont (1. Pg381, 2. Mfa1+Pg, 3. FimA+Pg, 4. MFB and 5. Un-infected control group).
Oral Pathobiont Activates Anti-Apoptotic Pathway, Promoting both Immune Suppression and Oncogenic Cell Proliferation.
No sample metadata fields
View SamplesGene expression profiling was carried out in six (wild type, ß2SP+/-, ß2SP-/-, SMAD3+/-, SMAD3-/- and ß2SP+/-/ SMAD3+/-) different mouse knockout embryonic fibroblast (MEF) cells. Beta-2-spectrin (ß2SP) is a dynamic intracellular non-pleckstrin homology (PH)-domain protein that belongs to a family of polypeptides that have been implicated in conferring cell polarity. Spectrins have been linked to multiple signaling pathways, including cell cycle regulation, DNA repair and TGFß signaling. In this study, we report a major role of the TGFß/Smad3 adaptor ß2-Spectrin in conserving genomic integrity from alcohol-induced DNA damage and describe a novel pathway that protects genomes from genotoxic stresses. To determine the mechanism for the oncogenic switch, and whether it is related to the role of ß2SP in TGF-ß signaling transduction or secondary to its cytoskeletal functions, we analyzed disruption of two elements of the TGF-ß pathway by generating double heterozygous Sptbn1+/-/Smad3+/- mice. Overall design: Whole-transcriptome RNA sequencing MEF cells of the following genotypes was carried out on an Illumina HiSeq 2000 sequencer: wildtype, heterozygous Beta-2-spectrin knockout (ß2SP+/-), homozygous Beta-2-spectrin knockout (ß2SP-/-), heterozygous SMAD3 (Mothers against decapentaplegic, Drosophila, Homolog of 3, SMAD3+/-), homozygous knockout SMAD3-/-, and double heterozygous mutation of Beta-2-spectrin and SMAD3 (ß2SP+/-/ SMAD3+/-).
TGF-β/β2-spectrin/CTCF-regulated tumor suppression in human stem cell disorder Beckwith-Wiedemann syndrome.
No sample metadata fields
View SamplesGene expression profiling was carried out in two liver tumors and one normal liver isolated from ß2SP+/-; SMAD3+/- mice, and one normal liver isolated from wild type mouse. Whole-transcriptome sequencing of these 4 liver tissues. Overall design: Whole-transcriptome RNA sequencing of the 4 different samples
TGF-β/β2-spectrin/CTCF-regulated tumor suppression in human stem cell disorder Beckwith-Wiedemann syndrome.
No sample metadata fields
View SamplesGene expression profiling was carried out in one normal human fibroblast cell line established from normal people and three different cell lines established from BWS patients to characterize the molecular mechanisms relevant to the etiology of BWS and tumor development. Whole-transcriptome sequencing of three BWS fibroblastic cell lines was established from patients with mutation in the CDKN1C mutation (CDKN1C+ cell line), and loss of methylation in the KCNQ1OT1 region (KvDMR+ cell line: with KvDMR molecular defect, and KvDMR- cell line: absence of KvDMR molecular defect but it had some clinical signs of BWS) Overall design: Whole-transcriptome RNA sequencing of the 4 different cell lines
TGF-β/β2-spectrin/CTCF-regulated tumor suppression in human stem cell disorder Beckwith-Wiedemann syndrome.
No sample metadata fields
View SamplesGene expression profiling was carried out in wild and ß2SP-/- (Sptbn1 -/-) mouse embryonic fibroblast (MEF) cells. Beta-2-spectrin (ß2SP) is a dynamic intracellular non-pleckstrin homology (PH)-domain protein that belongs to a family of polypeptides that have been implicated in conferring cell polarity. Spectrins have been linked to multiple signaling pathways, including cell cycle regulation, DNA repair and TGFß signaling. In this study, we report a major role of the TGFß/Smad3 adaptor ß2-Spectrin in conserving genomic integrity from alcohol-induced DNA damage and describe a novel pathway that protects genomes from genotoxic stresses. Overall design: Whole-transcriptome RNA sequencing of wild-type and ß2SP knockout (ß2SP-/-) mouse embryonic fibroblasts was carried out on an Illumina HiSeq 2000 sequencer. The raw data quality was assessed using a FastQC software. Adaptor presence was tested using Trimmomatic. The readings were then aligned to the NCBI mouse reference genome build 37.2 using the splice-aware aligner Tophat2 v2.0.10. Transcript quantification, normalization and assembly were carried out with Cufflinks. A gene model gtf file corresponding to the NCBI mouse reference genome build 37.2 was used in the quantification. Cuffdiff2, part of the Cufflinks suite of tools, was used to identify significant differences in gene expression profiles between the wild-type and ß2SP-/- MEF cells.
TGF-β/β2-spectrin/CTCF-regulated tumor suppression in human stem cell disorder Beckwith-Wiedemann syndrome.
No sample metadata fields
View Samples