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Homo sapiens
6 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
We profiled the global gene expression of human primary fetal lung fibroblasts (HFL-1) at different stages while they were undergoing replicative senescence
Publication Title
Bioinformatic framework for analysis of transcription factor changes as the molecular link between replicative cellular senescence signaling pathways and carcinogenesis.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 99 Downloadable Samples
Illumina HiSeq 2000
Description
The circadian regulation of transcriptional processes has a broad impact on cell metabolism. Here, we compared the diurnal transcriptome of human skeletal muscle conducted on serial muscle biopsies in vivo with profiles of human skeletal myotubes synchronized in vitro. Extensive rhythmic transcription was observed in human skeletal muscle in comparison to in vitro cell culture. However, nearly half of the in vivo rhythmicity was lost at the mRNA accumulation level. siRNA-mediated clock disruption in primary myotubes significantly affected the expression of ~8% of all genes, with impact on glucose homeostasis and lipid metabolism. Genes involved in GLUT4 expression, translocation and recycling were negatively affected, whereas lipid metabolic genes were altered to promote activation of lipid utilization. Moreover, basal and insulin stimulated glucose uptake were significantly reduced upon CLOCK depletion. Altogether, our findings suggest an essential role for cell-autonomous circadian clocks in coordinating muscle glucose homeostasis and lipid metabolism in humans. Overall design: 100 samples from 2 donors. Together with GSE108539, part of the same study described above.
Publication Title
Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscle.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Expression 430B Array (moe430b), Affymetrix Mouse Expression 430A Array (moe430a)
Description
RNA expression microarray analysis of prospermatogonia in 15 day post-conceptus (dpc) fetuses, a stage when they are undergoing rapid de novo DNA methylation. For comparison, we also analysed 15 dpc pachytene oogonia, 15 dpc female and male gonadal somatic cells, and adult pachytene spermatocytes.
Publication Title
RNA expression microarray analysis in mouse prospermatogonia: identification of candidate epigenetic modifiers.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
SOX9 is a transcriptional activator required for chondrogenesis, and SOX5 and SOX6 are closely related DNA-binding proteins that critically enhance its function. We used RNA-seq to charatierize a rat chondrosarcoma (RCS) cells as a faithful model for proliferating/early prehypertrophic growth plate chondrocytes and ChIP-seq to gain novel insights into the full spectrum of the target genes and modes of action of this chondrogenic trio. Overall design: RNAs were isolated from three bioogical replicatse of rat chondrosarcoma (RCS) cells and rib samples for RNA-seq experiments.
Publication Title
The transcription factors SOX9 and SOX5/SOX6 cooperate genome-wide through super-enhancers to drive chondrogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina Genome Analyzer II
Description
The hair of all mammals consists of terminally differentiated cells that undergo a specialized form of apoptosis called cornification. While DNA is destroyed during cornification, the extent to which RNA is lost is unknown. Here we find that multiple types of RNA are incompletely degraded after hair shaft formation in both mouse and human. Notably, mRNAs and short regulatory microRNAs (miRNAs) are stable in the hair as far as 10 cm from the scalp. To better characterize the post-apoptotic RNAs that escape degradation in the hair, we performed sequencing (RNA-seq) on RNA isolated from hair shafts pooled from several individuals. This hair shaft RNA library, which encompasses different hair types, genders, and populations, revealed 7,193 mRNAs, 449 miRNAs and thousands of unannotated transcripts that remain in the post-apoptotic hair. A comparison of the hair shaft RNA library to that of viable keratinocytes revealed surprisingly similar patterns of gene coverage and indicates that degradation of RNA is highly inefficient during apoptosis of hair lineages. The generation of a hair shaft RNA library could be used as months of accumulated transcriptional history useful for retrospective detection of disease, drug response and environmental exposure.
Publication Title
The post-apoptotic fate of RNAs identified through high-throughput sequencing of human hair.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 496 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Severe asthma is a collection of disease entities with varying pathophysiological characteristics (7) that result in symptoms of cough, wheeze and breathlessness, with frequent exacerbations. To address the problem of phenotypic difference and heterogeneity, the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project was set up as a public-private partnership within the framework of the Innovative Medicines Initiative (IMI), engaging academia, the pharmaceutical industry and patient groups. The goal of this investigation was to identify transcript fingerprints in whole blood that characterize patients with severe asthma and to determine whether subgroups of severe asthmatics can be identified. Furthermore, we were interested in elucidating the biological pathways that showed differences between subgroups.
Publication Title
A Severe Asthma Disease Signature from Gene Expression Profiling of Peripheral Blood from U-BIOPRED Cohorts.
Sample Metadata Fields
Sex, Specimen part, Race
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
CD74, a Type II membrane glycoprotein and MHC class II chaperone (Ii), is normally expressed by cells associated with the immune system. CD74 also forms heterodimers with CD44 to generate receptors to macrophage migration inhibitory factor (MIF), a proinflammatory cytokine. Following targeted Cre-mediated deletion of Ikk in IkkDeltaHep mice (a strain highly susceptible to chemically-induced hepatotoxicity and hepatocarcinogenesis), CD74 is abundantly expressed by hepatocytes throughout liver acini (as detected by specific Western blots and immunohistochemical stains); it is not observed in either control IkkF/F hepatocytes or embryonic fibroblasts from Ikk-/- mice. Constitutive CD74 expression in IkkDeltaHep hepatocytes is also accompanied by significantly augmented expression of CD44 and genes associated with antigen processing and host defense. These observations suggest that IkkDeltaHep hepatocytes might directly respond to MIF signaling, accounting partly for the enhanced susceptibility of IkkDeltaHep mice to hepatotoxins and hepatocarcinogens, and also might exhibit unusual immunological properties including antigen presentation.
Publication Title
Targeted deletion of hepatocyte Ikkbeta confers growth advantages.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The molecular processes underlying human milk production and the effects of mastitic infection are largely unknown because of limitations in obtaining tissue samples. Determination of gene expression in normal lactating women would be a significant step towards understanding why some women display poor lactation outcomes. Here we demonstrate the utility of RNA obtained directly from human milk cells to detect mammary epithelial cell (MEC)-specific gene expression. Milk cell RNA was collected from 5 time points (24 hours pre-partum during the colostrum period, mid lactation, two involution, and during a bout of mastitis) in addition to an involution series comprising three time points. Gene expression profiles were determined by use of human Affymetrix arrays. Milk cells collected during milk production showed that the most highly expressed genes were involved in milk synthesis (eg. CEL, OLAH, FOLR1, BTN1A1, ARG2), while milk cells collected during involution showed a significant down regulation of milk synthesis genes and activation of involution associated genes (eg. STAT3, NF-kB, IRF5, IRF7). Milk cells collected during mastitic infection revealed regulation of a unique set of genes specific to this disease state, whilst maintaining regulation of milk synthesis genes. Use of conventional epithelial cell markers was used to determine the population of MECs within each sample. This paper is the first to describe the milk cell transcriptome across the human lactation cycle and during mastitic infection, providing valuable insight into gene expression of the human mammary gland.
Publication Title
Analysis of human breast milk cells: gene expression profiles during pregnancy, lactation, involution, and mastitic infection.
Sample Metadata Fields
Specimen part
View Samples
GSE5587- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The Early Growth Response (Egr) family of transcription factors consists of 4 members (Egr1-4) that are expressed in a wide variety of cell types. A large body of evidence point to a role for Egr transcription factors in growth, survival, and differentiation. A major unanswered question is whether Egr transcription factors serve similar functions in diverse cell types by activating a common set of target genes. Signal transduction cascades in neurons and lymphocytes show striking parallels. Activation of either cell type activates the Ras-MAPK pathway and, in parallel, leads to increases in intracellular calcium stimulating the calcineurin-NFAT pathway. In both cell types, the strength of the activation signal affects the cellular outcomes and very strong stimuli lead to cell death. Notably both these pathways converge on the induction of Egr genes. We believe that downstream targets of Egr transcription factors in lymphocytes may also be activated by Egr factors in activated neurons. There is precedence for common target gene activation in these two cell types: apoptosis in both activated T cells and methamphetamine stimulated neurons occurs via FasL induction by NFAT transcription factors. We propose to use developing T lymphocytes (thymocytes) as a model system for discovery of Egr-dependent target genes for several reasons. First, we have observed a prominent survival defect in thymocytes from mice deficient in both Egr1 and Egr3 (1/3 DKO) and a partial differention block in the immature double negative (DN) stage. In addition, thymocytes are an easily manipulatable cell type, and the DN subpopulation affected in 1/3 DKO mice can be isolated to very high purity. We anticipate that 1/3 DKO thymocytes will provide an excellent experimental system that will provide insight into Egr-dependent transcription in neuronal development, activation, and death.
Publication Title
Redundant role for early growth response transcriptional regulators in thymocyte differentiation and survival.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 73 Downloadable Samples
- IlluminaHiSeq2500
Description
CSL is a key transcription factor, mostly acting as a repressor. While known as main effector of Notch signaling, it can also play Notch-independent functions. Despite the wide interest in CSL, the mechanisms responsible for its own regulation have been little studied. We recently showed that CSL down-modulation in human dermal fibroblasts (HDFs) leads to conversion into cancer associated fibroblasts, which promote keratinocyte tumor development. We show here that levels of CSL gene transcription differ among HDF strains derived from many different individuals, with negative correlation with genes involved in DNA damage/repair. CSL expression in all tested strains is negatively regulated by stress / DNA damaging insults caused by UVA, Reactive Oxygen Species (ROS), smoke extract and doxorubicin treatment. p53, a key effector of the DNA damage response, functions as common negative regulator of CSL gene transcription, through both suppression of CSL promoter activity and, indirectly, through increased p21 expression. CSL was previously shown to bind p53 suppressing its activity. The present findings indicate that p53, in turn, decreases CSL expression, which can serve to enhance p53 activity in the acute response of cells to DNA damaging cancer-threatening conditions. Overall design: RNA sequencing of 46 human foreskin fibroblasts
Publication Title
Negative control of CSL gene transcription by stress/DNA damage response and p53.
Sample Metadata Fields
No sample metadata fields
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