Filters
Technology
Platform
Mus musculus
10 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
A toxicogenomic analysis from liver of different pharmacological active coumarins (mammea A/BA+A/BB 3:1 and soulatrolide ) was performed on mice treated (20mg/kg/daily) for a whole week to evaluate if such compounds possess or could develop a hazardous profile on liver.
Publication Title
Toxicogenomic analysis of pharmacological active coumarins isolated from Calophyllum brasiliense.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus, Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Epigenetic pathways regulate gene expression by controlling and interpreting chromatin modifications. Cancer cells are characterized by altered epigenetic landscapes and commonly exploit the chromatin regulatory machinery to enforce oncogenic gene expression programs. While chromatin alterations are, in principle, reversible and often amendable to drug intervention, the promise of targeting such pathways therapeutically has been hampered by our limited understanding of cancer-specific epigenetic dependencies. Here we describe a non-biased approach to probe epigenetic vulnerabilities in acute myeloid leukemia (AML) an aggressive hematopoietic malignancy often associated with aberrant chromatin states. By screening a custom shRNA library targeting known chromatin regulators in a genetically defined AML mouse model, we identify the bromodomain-containing protein Brd4 as a critical requirement for disease maintenance. Suppression of Brd4 using shRNAs or the small-molecule inhibitor JQ1 led to robust anti-leukemic effects in vitro and in vivo, accompanied by terminal myeloid differentiation. Extensive evaluation of JQ1-sensitivity in primary human leukemia samples and in established cell lines revealed a broad activity of this compound against diverse AML subtypes. These effects are, at least in part, due to a requirement for Brd4 in maintaining Myc expression and promoting aberrant self-renewal. Together, our results indicate that Brd4 is a promising therapeutic target in AML and identify a small molecule that efficiently targets Myc. These findings also highlight the utility of RNAi screening as a discovery platform for revealing epigenetic vulnerabilities for direct pharmacologic intervention in cancer.
Publication Title
RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Target genes of Fbxl10 during 3T3-L1 adipogenesis was analyzed
Publication Title
The FBXL10/KDM2B scaffolding protein associates with novel polycomb repressive complex-1 to regulate adipogenesis.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Expression of the proendocrine gene neurogenin 3 (Ngn3) is required for the development of pancreatic islets. In order to better characterize the molecular events regulated by Ngn3 during development, we have determined the expression profile of differentiating murine embryonic stem cells (mESCs) uniformly induced to overexpress Ngn3. An ESC line was created that allows for the induction of Ngn3 by adding doxycycline (Dox) to the culture medium. Genome-wide microarray analysis was performed to identify genes regulated by Ngn3 in a variety of both undifferentiated and differentiated conditions. Characterization of pancreatic developmental markers during embryoid body (EB) formation revealed an optimum context for Ngn3 induction. Neuroendocrine genes including neurogenic differentiation 1 (NeuroD1) and single minded 1 (Sim1) were found to be significantly upregulated. Genes regulated by Ngn3 independent of the context were analyzed using systematic gene ontology tools and revealed Notch signaling as the most significantly regulated signaling pathway (p=0.009). This result is consistent with the hypothesis that Ngn3 expression makes the cell competent for Notch signaling to be activated and conversely, more sensitive to Notch signaling inhibition. Indeed, EBs induced to express Ngn3 were significantly more sensitive to gamma-secretase inhibitor-mediated Notch signaling inhibition (p<0.0001). Moreover, we find that Ngn3 induction in differentiating ESCs results in significant increases in insulin, glucagon, and somatostatin transcription.
Publication Title
Differentiation of embryonic stem cells conditionally expressing neurogenin 3.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE2531- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
In this experiment we compared total RNA from two commonly used choriocarcinoma cell lines, JEG3 and BeWo, to identify differentially expressed transcripts.
Publication Title
Microarray analysis of BeWo and JEG3 trophoblast cell lines: identification of differentially expressed transcripts.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
IonTorrentProton
Description
We describe a case of severe neonatal anemia with kernicterus due to compound heterozygosity for null mutations in KLF1, each inherited from asymptomatic parents. One of the mutations is novel. This is the first described case of a KLF1 null human. The phenotype of severe DAT-negative non-spherocytic hemolytic anaemia (NSHA), jaundice, hepato-splenomegaly, and marked erythroblastosis is more severe than that present in CDA type IV due to dominant mutations in the second zinc-finger of KLF1. There was a very high level of HbF expression into childhood (>70%), consistent with a key role for KLF1 in human hemoglobin switching. We performed RNA-seq on circulating erythroblasts and found human KLF1 acts like mouse Klf1 to coordinate expression of many genes required to build a red cell including those encoding globins, cytoskeletal components, AHSP, heme synthesis enzymes, cell cycle regulators, and blood group antigens. We identify novel KLF1 target genes including KIF23 and KIF11 which are required for proper cytokinesis. We also identify new roles for KLF1 in autophagy, global transcriptional control and RNA splicing. We suggest loss of KLF1 should be considered in otherwise unexplained cases of severe neonatal NSHA or hydrops fetalis. Overall design: mRNA sequencing on peripheral blood from a family trio (mother, father and proband) where parents were asymptomatic and proband had severe neonatal anemia.
Publication Title
KLF1-null neonates display hydrops fetalis and a deranged erythroid transcriptome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The current studies show that JMJD1A is phosphorylated at S265 by protein kinase A (PKA), and this is pivotal to activate expression of the b1-adrenergic receptor gene (Adrb1) and downstream targets including Ucp1. Phosphorylation of JMJD1A increases its interaction with the SWI/SNF nucleosome remodeling complex and DNA-bound PPARg. This complex conferred b-adrenergic-induced JMJD1A recruitment to target sites throughout the genome. Phospho-JMJD1A also facilitated long-range chromatin looping to recruit PPARg-bound distal-enhancers, SWI/SNF, and RNA polymerase close to the Adrb1 locus to activate transcription. Mutation of the PKA-phosphorylation site on JMJD1A abolished interactions with SWI/SNF without affecting demethylase activity suggesting the two functions are independent of each other. Our results show that JMJD1A demethylase is also a signal-sensing scaffold that regulates cAMP-responsive transcription via interactions with SWI/SNF and hormone stimulated higher-order chromatin conformational changes.
Publication Title
JMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via SWI/SNF association for thermogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 50 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
Recent studies of cortical pathology in secondary progressive multiple sclerosis have shown that a more severe clinical course and the presence of extended subpial grey matter lesions with significant neuronal/glial loss and microglial activation are associated with meningeal inflammation, including the presence of lymphoid-like structures in the subarachnoid space in a proportion of cases. To investigate the molecular consequences of pro-inflammatory and cytotoxic molecules diffusing from the meninges into the underlying grey matter, we carried out gene expression profiling analysis of the motor cortex from 20 post-mortem multiple sclerosis brains with and without substantial meningeal inflammation and 10 non-neurological controls. Gene expression profiling of grey matter lesions and normal appearing grey matter not only confirmed the substantial pathological cell changes, which were greatest in multiple sclerosis cases with increased meningeal inflammation, but also demonstrated the upregulation of multiple genes/pathways associated with the inflammatory response. In particular, genes involved in tumour necrosis factor (TNF) signalling were significantly deregulated in MS cases compared to controls.
Publication Title
Meningeal inflammation changes the balance of TNF signalling in cortical grey matter in multiple sclerosis.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
We identified distict mesodermal sub-populations based on Endoglin (Eng) and Flk1 expression in Brachyury (Bry) positive cells. By using whole-transcriptome analysis, we further characterized these populations and how they changed when Wnt pathway is inhibited Overall design: Reaggregates mRNA profiles of unsorted, Flk1+ Eng+, and Flk1- Eng+ samples were generated by deep sequencing, in triplicate , using Ilumina.
Publication Title
Endoglin integrates BMP and Wnt signalling to induce haematopoiesis through JDP2.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples GSE41509- Mus musculus, Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Restriction of intestinal stem cell expansion and the regenerative response by YAP.
Sample Metadata Fields
Specimen part, Treatment
View Samples