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GSE19624
Mus musculus
24 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
Endothelin-1 (ET-1), an endothelium-derived vasoconstrictor peptide, plays a role in the pathophysiology of cardiovascular disease. Transgenic mice that overexpress human preproET-1 selectively in the endothelium (eET-1) exhibit endothelial dysfunction, hypertrophic remodeling and vascular inflammation of resistance-size arteries in the absence of blood pressure elevation. To understand the mechanisms whereby ET-1 induces vascular damage, vascular gene expression using DNA microarrays was employed. RNA from mesenteric arteries of female and male young (6-7 weeks) and mature (6-8 months) eET-1 and wild type (WT) mice was isolated and changes in gene expression were determined by genome-wide expression profiling using Illumina microarray. This study revealed a set of genes potentially regulated by ET-1, which might be implicated in ET-1 induced-vascular damage.
Publication Title
Vascular gene expression in mice overexpressing human endothelin-1 targeted to the endothelium.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The choroid plexuses (ChPs) are the main regulators of cerebrospinal fluid (CSF) composition and thereby also control the composition of a principal source of signaling molecules that is in direct contact with neural stem cells in the developing brain. The regulators of ChP development mediating the acquisition of a fate that differs from the neighboring neuroepithelial cells are poorly understood. Here, we demonstrate in mice a crucial role for the transcription factor Otx2 in the development and maintenance of ChP cells. Deletion of Otx2 by the Otx2-CreERT2 driver line at E9 resulted in a lack of all ChPs, whereas deletion by the Gdf7-Cre driver line affected predominately the hindbrain ChP, which was reduced in size, primarily owing to an increase in apoptosis upon Otx2 deletion. Strikingly, Otx2 was still required for the maintenance of hindbrain ChP cells at later stages when Otx2 deletion was induced at E15, demonstrating a central role of Otx2 in ChP development and maintenance. Moreover, the predominant defects in the hindbrain ChP mediated by Gdf7-Cre deletion of Otx2 revealed its key role in regulating early CSF composition, which was altered in protein content, including the levels of Wnt4 and the Wnt modulator Tgm2. Accordingly, proliferation and Wnt signaling levels were increased in the distant cerebral cortex, suggesting a role of the hindbrain ChP in regulating CSF composition, including key signaling molecules. Thus, Otx2 acts as a master regulator of ChP development, thereby influencing one of the principal sources of signaling in the developing brain, the CSF.
Publication Title
The transcription factor Otx2 regulates choroid plexus development and function.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 10 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Naïve and primed pluripotency is characterized by distinct signaling requirements, transcriptomes and developmental properties, but both cellular states share key transcriptional regulators, Oct4, Sox2 and Nanog. Here we demonstrate that transition between these two pluripotent states is associated with widespread Oct4 relocalization, mirrored by global rearrangement of enhancer chromatin landscapes. Our genomic and biochemical analyses identified candidate mediators of primed state-specific Oct4 binding, including Otx2 and Zic2/3. Even in the absence of other differentiation cues, premature Otx2 overexpression is sufficient to exit the naïve state, induce transcription of a large subset of primed pluripotency-associated genes and redirect Oct4 to thousands of previously inaccessible sites. However, ability of Otx2 to engage new enhancer regions is determined by its levels, cis-encoded properties of the sites and signaling environment. Our results illuminate regulatory mechanisms underlying pluripotency and suggest that capacity of transcription factors such as Otx2 and Oct4 to function as pioneers is highly context-dependent Overall design: transcription profile of ESCs and EpiLCs to analzye changes during differentiation and the effect of Otx2 loss and overexpression on the differentiation properties
Publication Title
Reorganization of enhancer patterns in transition from naive to primed pluripotency.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Melanoma is an aggressive neoplasm with increasing incidence that is classified by the NCI as a recalcitrant cancer, i.e., a cancer with poor prognosis, lacking progress in diagnosis and treatment. In addition to conventional therapy, melanoma treatment is currently based on targeting the BRAF/MEK/ERK signaling pathway and immune checkpoints. As drug resistance remains a major obstacle to treatment success, advanced therapeutic approaches based on novel targets are still urgently needed. We reasoned that the base excision repair enzyme Thymine DNA Glycosylase (TDG) could be such a target for its dual role in safeguarding the genome and the epigenome, by performing the last of the multiple steps in DNA demethylation. Overall design: Six samples : cells treated with shTDG and cells treated with shControl both in triplicates.
Publication Title
Thymine DNA glycosylase as a novel target for melanoma.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Tri-methylation on histone H3 lysine 4 (H3K4me3) is enriched near transcription start sites and correlates with active transcription. Like other histone marks, methylation on H3K4 is catalyzed by the respective methyltransferases and erased by demethylases. Lysine demethylase 5 (KDM5) family of Fe (II) and a-ketoglutarate-dependent dioxygenases removes the methyl groups from H3K4me3. All four family members of KDM5 demethylases (KDM5A-D) share sequence identity, have similar in vitro kinetic parameters, and display functional redundancy. To determine the effects of complete depletion of KDM5 activity, we treated MCF7 cells with DMSO, or two pan-KDM5 specific inhibitors, KDM5-C70 (our lab code 443) and CPI-48 (our lab code 278) and performed RNA sequencing to determine gene expression changes after KDM5 inhibitor treatment. Overall design: RNA sequencing of MCF7 cells treated with DMSO or KDM5 inhibitors.
Publication Title
KDM5 histone demethylases repress immune response via suppression of STING.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
We use single-cell RNA-seq to determine distinct selection phenotypes of 2 rare thymic Treg cell progenitors as well as mature thymic Treg cells Overall design: A single cell suspension was generated from murine thymus then magnetically depleted for CD8/Ter119 before sorting CD25+Foxp3-, CD25-Foxp3lo and CD25+Foxp3+ cells from CD4+CD73- thymocytes on a BD Aria II. The 10x Genomic platform…
Publication Title
Thymic regulatory T cells arise via two distinct developmental programs.
Sample Metadata Fields
Age, Cell line, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
WNT1/beta-catenin signaling plays a crucial role in the generation of mesodiencephalic dopaminergic (mdDA) neurons including the Substantia nigra pars compacta (SNc) subpopulation, whose degeneration is a hallmark of Parkinsons Disease (PD). However, the precise functions of WNT/beta-catenin signaling in this context remain unknown. Using mutant mice, primary ventral midbrain (VM) cells and pluripotent stem cells (mouse embryonic stem cells and induced pluripotent stem cells), we show that Dickkopf 3 (DKK3), a secreted glycoprotein that modulates WNT/beta-catenin signaling, is specifically required for the correct differentiation of a rostrolateral mdDA precursor subset into SNc DA neurons.
Publication Title
Dickkopf 3 Promotes the Differentiation of a Rostrolateral Midbrain Dopaminergic Neuronal Subset In Vivo and from Pluripotent Stem Cells In Vitro in the Mouse.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- NextSeq 500
Description
The Iroquois homeodomain transcription factor gene IRX3 is highly expressed in the developing nervous system, limb buds and heart. In adults, expression levels specify risk of obesity. We now report a significant functional role for IRX3 in human acute leukemia. While transcript levels are very low in normal human bone marrow cell populations, high level IRX3 expression is observed in ~30% of patients with acute myeloid leukemia (AML), ~50% of patients with T-acute lymphoblastic leukemia and ~20% of patients with B-acute lymphoblastic leukemia, typically in association with high levels of HOXA9. Expression of IRX3 alone was sufficient to immortalise murine bone marrow stem and progenitor cells, and induce T- and B-lineage leukemias in vivo with incomplete penetrance. IRX3 knockdown induced terminal differentiation of AML cells. Combined IRX3 and Hoxa9 expression in murine bone marrow stem and progenitor cells substantially enhanced the morphologic and phenotypic differentiation block of the resulting AMLs by comparison with Hoxa9-only leukemias, through suppression of a myelomonocytic program. Likewise, in cases of primary human AML, high IRX3 expression is associated with reduced myelomonocytic differentiation. Thus, tissue-inappropriate derepression of IRX3 modulates the cellular consequences of HOX gene expression to enhance differentiation block in human AML. Overall design: Murine acute myeloid leukemias - 3 samples from separate mice with AML initiated by HOXA9 and 3 samples from separate mice with AML initiated by HOXA9 and IRX3 coexpression
Publication Title
Derepression of the Iroquois Homeodomain Transcription Factor Gene IRX3 Confers Differentiation Block in Acute Leukemia.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 724 Downloadable Samples
Illumina human-6 v2.0 expression beadchip, Affymetrix Human Genome U219 Array (hgu219)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Innate immune activity is detected prior to seroconversion in children with HLA-conferred type 1 diabetes susceptibility.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 356 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip, Affymetrix Human Genome U219 Array (hgu219)
Description
To unravel genes and molecular pathways involved in the pathogenesis of type 1 diabetes (T1D), we performed genome-wide gene expression profiling of prospective venous blood samples from children developing T1D-associated autoantibodies or progressing towards clinical diagnosis.
Publication Title
Innate immune activity is detected prior to seroconversion in children with HLA-conferred type 1 diabetes susceptibility.
Sample Metadata Fields
Sex, Specimen part
View Samples