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GSE26524
Mus musculus
3 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
ES cells differentiated in the presence of the Wnt inhibitor DKK1 fail to express the transcription factor Snail and undergo EMT or mesoderm differentiation. We generated an ES cell line, A2.snail, that induced Snail expression upon addition of doxycycline addition.
Publication Title
Snail promotes the cell-autonomous generation of Flk1(+) endothelial cells through the repression of the microRNA-200 family.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 278 Downloadable Samples
Illumina HiSeq 2500
Description
Aging is associated with functional decline of hematopoietic stem cells (HSC) as well as an increased risk of myeloid malignancies. We performed an integrative characterization of epigenomic and transcriptomic changes, including single-cell RNA-seq, during normal human aging. Lineage-CD34+CD38- cells (HSC-enriched, HSCe) undergo age-associated epigenetic reprogramming consisting of redistribution of DNA methylation and reductions in H3K27ac, H3K4me1 and H3K4me3. This reprogramming of aged HSCe globally targets developmental and cancer pathways which are comparably altered in AML of all ages; encompassing loss of 4,656 active enhancers, 3,091 bivalent promoters, and deregulation of several epigenetic modifiers and key hematopoietic transcription factors, such as KLF6, BCL6 and RUNX3. Notably, in vitro downregulation of KLF6 results in impaired differentiation, increased colony forming potential and changes in expression that recapitulate aging and leukemia signatures. Thus, age-associated epigenetic reprogramming may form a predisposing condition for the development of age-related AML. Overall design: We profiled the human HSCe (Lineage-, CD34+, CD38-) transcriptome with aging at the single cell level. Single-cell RNAseq was performed on FACS isolated human bone marrow derived HSCe from 5 young (24-37 yo) and 4 aged donor (64-71 yo). Donors had no known hematological malignancy.
Publication Title
Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
During gastrulation, cells of the prospective mesoderm ingress through the primitive streak and acquire fates based on complex spatial and temporal cues. Progenitors of the cardiogenic mesoderm are first found at E6.5 in the posterior lateral epiblast and subsequently migrate laterally and anteriorly to form the cardiac crescent at E7.5, when regionalized cell fates are first delineated . Lineage tracing and heterotopic transplantation studies suggest that precursors in the earliest heart field possess potential to generate myocardium, endocardium, and pericardium. The mechanisms by which inductive signals in the primitive streak effect the development of this pancardiac progenitor field, however, remain poorly understood
Publication Title
Mesp1 coordinately regulates cardiovascular fate restriction and epithelial-mesenchymal transition in differentiating ESCs.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 3000
Description
Aging is associated with functional decline of hematopoietic stem cells (HSC) as well as an increased risk of myeloid malignancies. We performed an integrative characterization of epigenomic and transcriptomic changes, including single-cell RNA-seq, during normal human aging. Lineage-CD34+CD38- cells (HSC-enriched, HSCe) undergo age-associated epigenetic reprogramming consisting of redistribution of DNA methylation and reductions in H3K27ac, H3K4me1 and H3K4me3. This reprogramming of aged HSCe globally targets developmental and cancer pathways which are comparably altered in AML of all ages; encompassing loss of 4,656 active enhancers, 3,091 bivalent promoters, and deregulation of several epigenetic modifiers and key hematopoietic transcription factors, such as KLF6, BCL6 and RUNX3. Notably, in vitro downregulation of KLF6 results in impaired differentiation, increased colony forming potential and changes in expression that recapitulate aging and leukemia signatures. Thus, age-associated epigenetic reprogramming may form a predisposing condition for the development of age-related AML. Overall design: CRISPR-Cas9 mediated knockout of KLF6 was performed in human peripheral blood CD34+ cells (n=4 replicates). RNA-seq was utilized to determine the effect of KLF6 knockout compared to a non-targeting control control.
Publication Title
Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Subject
View Samples- 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
- 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- 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- 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