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GSE37709
Homo sapiens
38 Downloadable Samples
Illumina HumanRef-8 v3.0 expression beadchip
Description
Gene expression analyis of two neonatal fibroblasts (BJ and HFF1), one adult dermal fibroblasts (NFH2), two BJ-derived human iPSCs (iB4 and iB5), two HFF1-derived iPSCs (iPS 2 and iPS4), four NFH2-derived iPSCs (OiPS3, OiPS6, OiPS8, OiPS16), one amniotic fluid cells and three derived iPSCs (lines 4, 5, 6, 10, and 41), two human ES cells (H1 and H9), neonatal fibroblasts transduced with the four retroviral factors (OKSM) after 24h, 48h, and 72h, neonatal fibroblasts treated with EDHB for 24h, 48h, and 72h, neonatal fibroblasts transduced with four factors and treated with EDHB for 24h, 48h, and 72h, neonatal fibroblasts knocked down for HIF1A (HIF1-KD) and for a scrambled sequence (SCR-KD)
Publication Title
HIF1α modulates cell fate reprogramming through early glycolytic shift and upregulation of PDK1-3 and PKM2.
Sample Metadata Fields
Age, Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Cytoplasmic DNA triggers the activation of the innate immune system. While downstream signaling components have been characterized, the DNA sensing components remain largely elusive. We performed a systematic proteomics screen for proteins that associate with DNA, traversed to a screen for IFN--induced transcripts. We identified DSIRE (DNA sensor for the IL-1 response, previously called AIM2) as a candidate cytoplasmic sensor. DSIRE showed a marked selectivity for double-stranded DNA. DSIRE can recruit the inflammasome adaptor ASC and gets redistributed to ASC speckles upon coexpression of ASC. RNAi-mediated reduction of DSIRE expression led to an impairment in IL-1 maturation. Reconstitution of unresponsive cells with DSIRE, ASC, caspase 1 and IL-1 showed that DSIRE is sufficient for inflammasome activation. Overall, our data strongly suggest that DSIRE is a cytoplasmic DNA sensor for the inflammasome.
Publication Title
An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Activity-dependent gene expression is central for sculpting neuronal connectivity in the brain. Despite the importance for synaptic plasticity, a comprehensive analysis of the temporal changes in the transcriptomic response to neuronal activity is lacking. In a genome wide survey we identified genes that were induced at 1, 4, 8, or 24 hours following neuronal activity in the hippocampus.
Publication Title
Genome-wide profiling of the activity-dependent hippocampal transcriptome.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
An immediate-late gene expression module decodes ERK signal duration.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We integrate experimental data and mathematical modelling to unveil how ERK signal duration is relayed to mRNA dynamics.
Publication Title
An immediate-late gene expression module decodes ERK signal duration.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The goal of this study is to determine the effects of adipose-specific Glut4 overexpression or knockout on changes in adipose tissue global gene expression
Publication Title
A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2000
Description
Understanding how regulatory sequences interact in the context of chromosomal architecture is a central challenge in biology. Chromosome conformation capture revealed that mammalian chromosomes possess a rich hierarchy of structural layers, from multi-megabase compartments to sub-megabase topologically associating domains (TADs), and further down to sub-TAD loop domains. TADs appear to act as regulatory microenvironments by constraining and segregating regulatory interactions across discrete chromosomal regions. However, it is unclear whether other (or all) folding layers share similar properties, or rather TADs constitute a privileged folding scale with maximal impact on the organization of regulatory interactions. Here we present a novel parameter-free algorithm (CaTCH) that identifies hierarchical trees of chromosomal domains in Hi-C maps, stratified through their reciprocal physical insulation which is a simple and biologically relevant property. By applying CaTCH to published Hi-C datasets, we show that previously reported folding layers appear at different insulation levels. We demonstrate that although no structurally privileged folding level exists, TADs emerge as a functionally privileged scale defined by maximal enrichment of CTCF at boundaries, and maximal cell-type conservation. By measuring transcriptional output in embryonic stem cells and neural precursor cells, we show that TADs also maximize the likelihood that genes in a domain are co-regulated during differentiation. Finally, we observe that regulatory sequences occur at genomic locations corresponding to optimized mutual interactions at the scale of TADs. Our analysis thus suggests that the architectural functionality of TADs arises from the interplay between their ability to partition interactions and the genomic position of regulatory sequences. Overall design: The hybrid mouse ESC line F1-21.6 (129Sv-Cast/EiJ), previously described in (Jonkers et al., 2009), were grown on mitomycin C-inactivated MEFs in ES cell media containing 15% FBS (Gibco), 10-4 M b-mercaptoethanol (Sigma), and 1000U/ml of leukaemia inhibitory factor (LIF, Chemicon). Mouse ES cells were differentiated into neural progenitor cells (NPC) as previously described (Conti et al., 2005; Splinter et al., 2011). Total RNAs were prepared by Trizol extraction from the mouse ESC line, and for one NPC clone derived from it. Two biological replicates were collected for ESCs and NPCs. After ribosomal RNA depletion with Ribo-Zero (Illumina), RNA-seq libraries were prepared using ScriptSeq v2 kit (Illumina) following the manufacturer’s instructions. Libraries were prepared in two technical replicates per biological replicate. 50 bp single-end sequencing was performed on Illumina HiSeq 2000 instruments according to manufacturer’s instructions.
Publication Title
Reciprocal insulation analysis of Hi-C data shows that TADs represent a functionally but not structurally privileged scale in the hierarchical folding of chromosomes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HiSeq 2000
Description
Aberrant cell signaling can cause cancer and other diseases and is a focal point of drug research. A common approach is to infer signaling activity of pathways from gene expression. However, mapping gene expression to pathway components disregards the effect of post-translational modifications, and downstream signatures represent very specific experimental conditions. Here we present PROGENy, a method that overcomes both limitations by leveraging a large compendium of publicly available perturbation experiments to yield a common core of Pathway RespOnsive GENes. Unlike existing methods, PROGENy can (i) recover the effect of known driver mutations, (ii) provide or improve strong markers for drug indications, and (iii) distinguish between oncogenic and tumor suppressor pathways for patient survival. Collectively, these results show that PROGENy accurately infers pathway activity from gene expression. Overall design: HEK293?RAF1:ER cells were treated with different stimuli (4OHT, Ly29002, TNFa, TGF1b, IFNg) for different periods of time (1h, 4h).
Publication Title
Perturbation-response genes reveal signaling footprints in cancer gene expression.
Sample Metadata Fields
Specimen part, Subject
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Reverse engineering a hierarchical regulatory network downstream of oncogenic KRAS.
Sample Metadata Fields
Cell line, Treatment
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
RAS mutations are highly relevant for progression and therapy response of human tumours, but the genetic network that ultimately executes the oncogenic effects is poorly understood. Here we used a reverse-engineering approach in an ovarian cancer model to reconstruct KRAS oncogene-dependent cytoplasmic and transcriptional networks from perturbation experiments based on gene silencing and pathway inhibitor treatments. We measured mRNA and protein levels in manipulated cells by microarray, RT-PCR and Western Blot analysis, respectively. The reconstructed model revealed complex interactions among the transcriptional and cytoplasmic components, some of which were confirmed by double pertubation experiments. Interestingly, the transcription factors decomposed into two hierarchically arranged groups. To validate the model predictions we analysed growth parameters and transcriptional deregulation in the KRAS-transformed epithelial cells. As predicted by the model, we found two functional groups among the selected transcription factors. The experiments thus confirmed the predicted hierarchical transcription factor regulation and showed that the hierarchy manifests itself in downstream gene expression patterns and phenotype.
Publication Title
Reverse engineering a hierarchical regulatory network downstream of oncogenic KRAS.
Sample Metadata Fields
Cell line, Treatment
View Samples