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GSE24150
Homo sapiens
1 Downloadable Sample
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray based mRNA profiling was used to identify the mechanism of action for the small molecule b-AP15.
Publication Title
Inhibition of proteasome deubiquitinating activity as a new cancer therapy.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
NextSeq 500
Description
The Nucleosome Remodeling and Deacetylase (NuRD) complex plays an important role in gene expression regulation, stem cell self-renewal, and lineage commitment. Yet little is known about the dynamics of NuRD during cellular differentiation. Here, we study these dynamics using genome-wide profiling and quantitative interaction proteomics in mouse embryonic stem cells (ESCs) and neural progenitor cells (NPCs). The genomic targets of NuRD are highly dynamic during differentiation, with most binding occurring at cell-type specific promoters and enhancers. We identify ZFP296 as a novel, ESC-specific NuRD interactor that also interacts with the SIN3A complex. ChIP-sequencing in Zfp296 knockout (KO) ESCs reveals decreased NuRD binding both genome-wide and at ZFP296 binding sites, although this has little effect on the transcriptome. Nevertheless, Zfp296 KO ESCs exhibit delayed induction of lineage-specific markers upon differentiation to embryoid bodies. In summary, we identify an ESC-specific NuRD interacting protein which regulates genome-wide NuRD binding and cellular differentiation. Overall design: RNA-seq samples of wildtype R1 ESCs and Zfp296 CRISPR KO clone 2 R1 ESCs
Publication Title
NuRD-interacting protein ZFP296 regulates genome-wide NuRD localization and differentiation of mouse embryonic stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We performed microarray analysis to investigate the gene expression profile changes induced by Hmg20b knock down in I/11 cells.
Publication Title
The DNA binding factor Hmg20b is a repressor of erythroid differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 21 Downloadable Samples
Description
RNA modifications are integral to regulation of RNA metabolism. One such abundant mRNA modification is m6A, which impacts various aspects of RNA metabolism including splicing, transport and degradation. Current knowledge about proteins recruited to m6A to carry out these molecular processes is still limited. Here we describe a comprehensive and systematic mass spectrometry-based screening of m6A interactors in various cell types and species. Amongst the main findings, we identified G3BP1 as a protein, which is repelled by m6A and which positively regulates mRNA stability in an m6A regulated manner. Furthermore, we identified FMR1 as a novel, RNA sequence context dependent m6A reader, thus revealing a connection between an mRNA modification and an autism spectrum disorder. Collectively, our data represents a rich resource for the community and sheds further light on the complex interplay between m6A, m6A interactors and mRNA homeostasis. Overall design: Transcriptome wide profiling of G3BP1 and G3BP2 binding sites and mRNA half-live measurement after G3BP1 overexpression or knockdown.
Publication Title
N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) recruits and repels proteins to regulate mRNA homeostasis.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Vitamin A is the only known compound that produces spontaneous fractures in rats. In an effort to resolve the molecular mechanism behind this effect, we fed young rats high doses of vitamin A and performed a global transcriptional analysis of diaphyseal bone after one week, i.e. just before the first fractures appeared. Microarray gene expression analysis revealed that 68 transcripts were differentially expressed in hypervitaminotic cortical bone and 118 transcripts were found when the bone marrow was also included. 98% of the differentially expressed genes in the bone marrow sample were up-regulated. In contrast, hypervitaminotic cortical bone without marrow showed reduced expression of 37% of differentially expressed genes. Gene Ontology (GO) analysis revealed that only samples containing bone marrow were associated to a GO term, which principally represented extracellular matrix (ECM). This is consistent with the histological findings of increased endosteal bone formation. Four of the genes in this ECM cluster and four other genes, including Cyp26b1 which is known to be up-regulated by vitamin A, were selected and verified by real-time PCR. In addition, immunohistochemical staining of bone sections confirmed that the bone-specific molecule, osteoadherin (Omd) was up-regulated. Further analysis of the major gene expression changes revealed distinct differences between cortical bone and bone marrow, e.g. there appeared to be augmented Wnt signaling in the bone marrow but reduced Wnt signaling in cortical bone. Moreover, induced expression of hypoxia-associated genes was only found in samples containing bone marrow. Together, these results corroborate our previous observations of compartment-specific effects of vitamin A, with reduced periosteal but increased endosteal bone formation, and suggest important roles for Wnt signaling and hypoxia in the processes leading to spontaneous fractures.
Publication Title
Microarray profiling of diaphyseal bone of rats suffering from hypervitaminosis A.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Homo sapiens
- 3 Downloadable Samples
- NextSeq 500
Description
The NuRD complex is generally thought to repress transcription at both hyper- and hypomethylated regions in the genome. In addition, the complex is involved in the DNA damage response. Here, we show that ZMYND8 bridges NuRD to a number of putative DNA-binding zinc finger proteins. The ZMYND8 MYND domain directly interacts with PPPL? motifs in the NuRD subunit GATAD2A. Furthermore, GATAD2A and GATAD2B exclusively form homodimers and they thus define mutually exclusive NuRD subcomplexes. ZMYND8 and MBD3 share a large number of genome-wide binding sites, mostly active promoters and enhancers. Depletion of ZMYND8 does not affect NuRD occupancy genome-wide and expression of NuRD/ZMYND8 target genes in steady-state asynchronous cells. However, ZMYND8 facilitates immediate recruitment of GATAD2A/NuRD to induced sites of DNA damage. These results thus show that a specific substoichiometric interaction with a NuRD subunit paralogue provides unique functionality to a distinct NuRD subcomplex. Overall design: RNA-seq samples for HeLa FRT-TO mock, ZMYND8KO, and ZMYND8KO-rescue cells
Publication Title
ZMYND8 Co-localizes with NuRD on Target Genes and Regulates Poly(ADP-Ribose)-Dependent Recruitment of GATAD2A/NuRD to Sites of DNA Damage.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
Organoid technology provides the possibility to culture human colon tissue and patient-derived colorectal cancers (CRC) while maintaining all functional and phenotypic characteristics. Labeling of human colon stem cells (CoSCs), especially in normal and benign tumor organoids, is challenging and therefore limits usability of multi-patient organoid libraries for CoSC research. Here, we developed STAR (STem cell Ascl2 Reporter), a minimal enhancer/promoter element that reports transcriptional activity of ASCL2, a master regulator of LGR5+ CoSC fate. Among others via lentiviral infection, STAR minigene labels stem cells in normal as well as in multiple engineered and patient-derived CRC organoids of different stage and genetic make-up. STAR revealed that stem cell driven differentiation hierarchies and the capacity of cell fate plasticity (de-differentiation) are present at all stages of human CRC development. The flexible and user-friendly nature of STAR applications in combination with organoid technology will facilitate basic research on human adult stem cell biology. Overall design: Cells from different colon organoid types were FACS sorted for stem STemness Ascl2 Reporter activity for transcriptome profiling by RNA-seq.
Publication Title
Specific Labeling of Stem Cell Activity in Human Colorectal Organoids Using an ASCL2-Responsive Minigene.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The specific contribution of the two TNF-receptors Tnfr1 and Tnfr2 to TNF-induced inflammation in the glomerulus is unknown. In mice, TNF exposure induces glomerular expression of inflammatory mediators like adhesion molecules and chemokines in vivo, and glomerular accumulation of leukocytes.
Publication Title
Distinct contributions of TNF receptor 1 and 2 to TNF-induced glomerular inflammation in mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 57 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Sepsis is a clinical syndrome that can be caused by bacteria or fungi. Early knowledge on the nature of the causative agent is a prerequisite for targeted anti-microbial therapy. Besides currently used detection methods like blood culture and PCR-based assays, the analysis of the transcriptional response of the host to infecting organisms holds great promise. In this study, we aim to examine the transcriptional footprint of infections caused by the bacterial pathogens Staphylococcus aureus and Escherichia coli and the fungal pathogens Candida albicans and Aspergillus fumigatus in a human whole-blood model. Moreover, we use the expression information to build a random forest classifier to determine if the pathogen is bacterial, fungal or neither of the two. After normalizing the transcription intensities using stably expressed reference genes, we filtered the gene set for biomarkers of bacterial or fungal blood infections. This selection is based on differential expression and an additional gene relevance measure. In this way, we identified 38 biomarker genes, including IL6, SOCS3, and IRG1 which were already associated to sepsis by other studies. Using these genes, we trained the classifier and assessed its performance. It yielded a 96% accuracy (sensitivities >93%, specificities >97%) for a 10-fold stratified cross-validation and a 92% accuracy (sensitivities and specificities >83%) for an additional dataset comprising Cryptococcus neoformans infections. Furthermore, the noise-robustness of the classifier suggests high rates of correct class predictions on datasets of new species. In conclusion, this genome-wide approach demonstrates an effective feature selection process in combination with the construction of a well-performing classification model. Further analyses of genes with pathogen-dependent expression patterns can provide insights into the systemic host responses, which may lead to new anti-microbial therapeutic advances.
Publication Title
Biomarker-based classification of bacterial and fungal whole-blood infections in a genome-wide expression study.
Sample Metadata Fields
Sex, Specimen part, Subject, Time
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Maternal obesity during the pre-implantation period leads to a pro-inflammatory milieu in the ovaries. We conducted a global transcriptomic profiling in ovaries from TEN fed rats during the pre-implantation period. Microarray analysis revealed that obesity lead to increased expression of genes related to inflammation, decreased glucose transporters, and dysregulation of ovarian function-related genes in the ovaries. Our results suggest maternal obesity led to an up-regulation of inflammatory genes and Egr-1 protien expression in peri-implantation ovarian tissue, and a concurrent down-regulation of glucose transporters mRNA and AKT and PI3K protein levels.
Publication Title
Maternal obesity is associated with ovarian inflammation and upregulation of early growth response factor 1.
Sample Metadata Fields
Sex, Specimen part
View Samples