Filters
Technology
Platform
SRP174051
Mus musculus
12 Downloadable Samples
Illumina Genome Analyzer
Description
Glucocorticoid resistance (GCR) is defined as an unresponsiveness to the anti-inflammatory properties of glucocorticoids (GCs) and their receptor, the glucocorticoid receptor (GR). It is a serious problem in the management of inflammatory diseases and occurs frequently. The strong pro-inflammatory cytokine TNF induces an acute form of GCR, not only in mice, but also in several cell lines, e.g. in the hepatoma cell line BWTG3, as evidenced by impaired Dexamethasone (Dex)-induced GR-dependent gene expression. We report that TNF has a significant and broad impact on the transcriptional performance of GR, but no impact on nuclear translocation, dimerization or DNA binding capacity of GR. Proteome-wide proximity-mapping (BioID), however, revealed that the GR interactome is strongly modulated by TNF. One GR cofactor that interacts significantly less with the receptor under GCR conditions is p300. NF?B activation and p300 knockdown both reduce transcriptional output of GR, whereas p300 overexpression and NF?B inhibition revert TNF-induced GCR, which is in support of a cofactor reshuffle model. This hypothesis is supported by FRET studies. This mechanism of GCR opens new avenues for therapeutic interventions in GCR diseases Overall design: Examination of GR induced gene expression in 4 conditions (1 control: NI and 3 treated: DEX, TNF, TNFDEX) starting from 3 biological replicates
Publication Title
TNF-α inhibits glucocorticoid receptor-induced gene expression by reshaping the GR nuclear cofactor profile.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Arabidopsis thaliana
- 9 Downloadable Samples
Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
This experiment was set up in order to identify the (direct) transcriptional targets of the Ethylene Response Factor 115 (ERF115) transcription factor. Because ERF115 expression occurs in quiescent center (QC) cells and strong effects on the QC cells were observed in ERF115 overexpression plants, root tips were harvested for transcript profiling in order to focus on root meristem and QC specific transcriptional targets.
Publication Title
ERF115 controls root quiescent center cell division and stem cell replenishment.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
To understand how haploinsufficiency of progranulin (PGRN) protein causes frontotemporal dementia (FTD), we created induced pluripotent stem cells (iPSC) from patients carrying the GRNIVS1+5G>C mutation (FTD-iPSCs). FTD-iPSCs were fated to cortical neurons, the cells most affected in FTD and known to express PGRN. Although generation of neuroprogenitors was unaffected, their further differentiation into neurons, especially CTIP2-, FOXP2- or TBR1-TUJ1 double positive cortical neurons, was significantly decreased in FTD-neural progeny. Zinc finger nuclease-mediated introduction of PGRN cDNA into the AAVS1 locus corrected defects in cortical neurogenesis, demonstrating that PGRN haploinsufficiency causes inefficient cortical neuron generation. RNAseq analysis confirmed reversal of altered gene expression profile following genetic correction. Wnt signaling pathway, one of the top defective pathways in FTD-iPSC-derived neurons coupled with its reversal following genetic correction, makes it an important candidate. Therefore, we demonstrate for the first time that PGRN haploinsufficiency hampers corticogenesis in vitro. Overall design: We profiled 6 samples: two biological replicates for 3 conditions. Condition 1 consists of neuronal progeny derived from human Embryonic Stem Cells. Condition 2 consists of neuronal progeny derived from induced pluripotent stem cells generated from patients carrying PGRN mutation. Condition 3 consists of neuronal progeny derived from induced pluripotent stem cells generated from patients carrying PGRN mutation, genetically modified to correct the PGRN defect.
Publication Title
Restoration of progranulin expression rescues cortical neuron generation in an induced pluripotent stem cell model of frontotemporal dementia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
We sequenced mRNA from 6 samples of FACsorted telencephalons from E14.5 Sip1|Nkx2-1 knockout and WT|Nkx2-1 control mouse embryos to find differentially expressed genes in the absence of the transcription factor Sip1. Overall design: Examination of mRNA levels in 3 control and 3 Sip1|Nkx2-1 knockout samples
Publication Title
Directed migration of cortical interneurons depends on the cell-autonomous action of Sip1.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Macaca mulatta
- 8 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
In vitro oocyte maturation (IVM) holds great promise as a tool for enhancing clinical treatment of infertility, enhancing availability of non human primates for development of disease models, and facilitating endangered species preservation. However, IVM outcomes have remained significantly below success rates obtained using in vivo matured (VVM) oocytes from humans and non human primates. A cDNA array based analysis is presented, comparing the transcriptomes of VVM oocytes with IVM oocytes. We observe a small set of just 59 mRNAs that are differentially expressed between the two cell types. These mRNAs are related to cellular homeostasis, cell-cell interactions including growth factor and hormone stimulation and cell adhesion, and other functions such as mRNA stability and translation. Additionally, we observe in IVM oocytes overexpression of PLAGL1 and MEST, two maternally imprinted genes, indicating a possible interruption or loss of correct epigenetic programming. These results indicate that, under certain IVM conditions, oocytes that are molecularly highly similar to VVM oocytes can be obtained, however the interruption of normal oocyte-somatic cell interactions during the final hours of oocyte maturation may preclude the establishment of full developmental competence.
Publication Title
Effects of in vitro maturation on gene expression in rhesus monkey oocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2000
Description
Genetic studies in T-cell acute lymphoblastic leukemia have uncovered a remarkable complexity of oncogenic and loss-of-function mutations. Amongst this plethora of genetic changes, NOTCH1 activating mutations stand out as the most frequently occurring genetic defect, identified in more than 50% of T-cell acute lymphoblastic leukemias, supporting an essential driver role for this gene in T-cell acute lymphoblastic leukemia oncogenesis. In this study, we aimed to establish a comprehensive compendium of the long non-coding RNA transcriptome under control of Notch signaling. For this purpose, we measured the transcriptional response of all protein coding genes and long non-coding RNAs upon pharmacological Notch inhibition in the human T-cell acute lymphoblastic leukemia cell line CUTLL1 using RNA-sequencing. Similar Notch dependent profiles were established for normal human CD34+ thymic T-cell progenitors exposed to Notch signaling activity in vivo. In addition, we generated long non-coding RNA expression profiles (array data) from GSI treated T-ALL cell lines, ex vivo isolated Notch active CD34+ and Notch inactive CD4+CD8+ thymocytes and from a primary cohort of 15 T-cell acute lymphoblastic leukemia patients with known NOTCH1 mutation status. Integration of these expression datasets with publically available Notch1 ChIP-sequencing data resulted in the identification of long non-coding RNAs directly regulated by Notch activity in normal and malignant T-cell context. Given the central role of Notch in T-cell acute lymphoblastic leukemia oncogenesis, these data pave the way towards development of novel therapeutic strategies that target hyperactive Notch1 signaling in human T-cell acute lymphoblastic leukemia. Overall design: CUTLL1 cell lines were treated with Compound E (GSI) or DMSO (solvent control). Cells were collected 12 h and 48 h after treatment. This was performed for 3 replicates. RNA-sequencing was performed on these samples.
Publication Title
The Notch driven long non-coding RNA repertoire in T-cell acute lymphoblastic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The goal of this study was to gain insight into the molecular heterogeneity of capillary endothelial cells derived from different organs by microarray profiling of freshly isolated cells and identify transcription factors that may determine the specific gene expression profile of endothelial cells from different tissues. The study focused on heart endothelial cells and presents a validated signature of 31 genes that are highly enriched in heart endothelial cells. Within this signature 5 transcription factors were identified and the optimal combination of these transcription factors was determined for specification of the heart endothelial fingerprint.
Publication Title
Meox2/Tcf15 heterodimers program the heart capillary endothelium for cardiac fatty acid uptake.
Sample Metadata Fields
Sex, Specimen part
View Samples- 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
Genome-wide promoter methylation analysis in neuroblastoma identifies prognostic methylation biomarkers.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 15 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
8 neuroblastoma (NB) cell lines (CLB-GA, IMR-32, SH-SY5Y, N206, CHP-902R, LAN-2, SK-N-AS, SJNB-1) were profiled on the Affymetrix HGU-133plus2,0 platform before and after treatment with DAC (2'-deoxy-5-azacytidine) to investigate the influence on expression after inhibiting DNA-methylation
Publication Title
Genome-wide promoter methylation analysis in neuroblastoma identifies prognostic methylation biomarkers.
Sample Metadata Fields
Treatment
View Samples- Macaca mulatta
- 8 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Follicular somatic cells (mural granulosa cells and cumulus cells) and the oocyte communicate through paracrine interactions and through direct gap junctions between oocyte and cumulus cells. Considering that mural and cumulus cells arise through a common developmental pathway and that their differentiation is essential to reproductive success, understanding how these cells differ is a key aspect to understanding their critical functions. Changes in global gene expression before and after an ovulatory stimulus were compared between cumulus and mural granulosa cells to test the hypothesis that mural and cumulus cells are highly differentiated at the time of an ovulatory stimulus and further differentiate during the periovulatory interval. The transcriptomes of the two cell types were markedly different (>1500 genes) before an ovulatory hCG bolus but converged after ovulation to become completely overlapping. The predominant transition was for the cumulus cells to become more like mural cells after hCG. This indicates that the differentiated phenotype of the cumulus cell is not stable and irreversibly established but may rather be an ongoing physiological response to the oocyte.
Publication Title
Rhesus monkey cumulus cells revert to a mural granulosa cell state after an ovulatory stimulus.
Sample Metadata Fields
Specimen part
View Samples