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SRP032928
Homo sapiens
7 Downloadable Samples
IlluminaHiSeq2000
Description
Down syndrome (trisomy 21) is the most common viable chromosomal disorder with intellectual impairment and several other developmental abnormalities. Here, we report the generation and characterization of induced pluripotent stem cells (iPSCs) derived from monozygotic twins discordant for trisomy 21 in order to eliminate the effects of the variability of genomic background. The alterations observed by genetic analysis at the iPSC level and at first approximation in early development illustrate the developmental disease transcriptional signature of Down syndrome. Moreover, we observed an abnormal neural differentiation of Down syndrome iPSCs in vivo when formed teratoma in NOD-SCID mice, and in vitro when differentiated into neuroprogenitors and neurons. These defects were associated with changes in the architecture and density of neurons, astroglial and oligodendroglial cells together with misexpression of genes involved in neurogenesis, lineage specification and differentiation. Furthermore, we provide novel evidence that dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) on chromosome 21 likely contribute to these defects. Importantly, we found that targeting DYRK1A pharmacologically or by shRNA results in a considerable correction of these defects. Overall design: mRNA-seq profiling of iPS cells (4 euploid and 3 trisomy 21) derived from fibroblasts of monozygotic twins discordant for trisomy 21
Publication Title
Modelling and rescuing neurodevelopmental defect of Down syndrome using induced pluripotent stem cells from monozygotic twins discordant for trisomy 21.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Pluripotency-related, valproic acid (VPA)-induced genome-wide histone H3 lysine 9 (H3K9) acetylation patterns in embryonic stem cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene expression profiles of E14 embryonic stem cells (ESCs) before and after treatment with low levels of the histone deacetylase (HDAC) inhibitors valproic acid (VPA) and sodium butyrate (NaBu).
Publication Title
Pluripotency-related, valproic acid (VPA)-induced genome-wide histone H3 lysine 9 (H3K9) acetylation patterns in embryonic stem cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene expression profiles of E14 embryonic stem cells (ESCs) before and after treatment with low levels of the histone deacetylase (HDAC) inhibitor valproic acid (VPA).
Publication Title
Pluripotency-related, valproic acid (VPA)-induced genome-wide histone H3 lysine 9 (H3K9) acetylation patterns in embryonic stem cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
External stimulations of cells by hormones, growth factors or cytokines activate signal transduction pathways that subsequently induce a rearrangement of cellular gene expression. The representation and analysis of changes in the gene response is complicated, and essentially consists of multiple layered temporal responses. In such situations, matrix factorization techniques may provide efficient tools for the detailed temporal analysis. Related methods applied in bioinformatics intentionally do not take prior knowledge into account. In signal processing, factorization techniques incorporating data properties like second-order spatial and temporal structures have shown a robust performance. However, large-scale biological data rarely imply a natural order that allows the definition of an autocorrelation function. We therefore develop the concept of graph-autocorrelation. We encode prior knowledge like transcriptional regulation, protein interactions or metabolic pathways as a weighted directed graph. By linking features along this underlying graph, we introduce a partial ordering of the samples to define an autocorrelation function. Using this framework as constraint to the matrix factorization task allows us to set up the fast and robust graph decorrelation (GraDe) algorithm. To analyze the alterations in the gene response in IL-6 stimulated primary mouse hepatocytes by GraDe, a time-course microarray experiment was performed. Extracted gene expression profiles show that IL-6 activates genes involved in cell cycle progression and cell division in a time-resolved manner. On the contrary, genes linked to metabolic and apoptotic processes are down-regulated indicating that IL-6 mediated priming rendered hepatocytes more responsive towards cell proliferation and reduces expenses for the energy household.
Publication Title
Knowledge-based matrix factorization temporally resolves the cellular responses to IL-6 stimulation.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Smoking is a major risk factor for Urothelial carcinoma (UC). However the complex mechanisms, how smoking promotes carcinogenesis and tumour progression, remain obscure. A microarray based approached was therefore performed to detect the smoking derived gene expression alteration in non-malignant and malignant urothelial tissues from patients with superficial or invasive UC. Smoking enhanced cell migration and response to tissue damages. In non-malignant tissues smoking induced immune response and altered the cytoskeleton. In urothelial carcinoma, smoking altered extracellular and chromosome structures. Smoking affected tissues from patients with invasive carcinomamore strongly, up-regulating particularly growth factors and oncogenes in non-malignant tissue of patients with invasive but not with superficial carcinoma. In former smokers, comparable changes were seen in tissues form patients with invasive disease while they were minor or reversed in tissue of patients with superficial disease. Best but not complete tissue repair was suggestedfor non-malignant tissue from patients with superficial tumours.
Publication Title
New insights into the influence of cigarette smoking on urothelial carcinogenesis: smoking-induced gene expression in tumor-free urothelium might discriminate muscle-invasive from nonmuscle-invasive urothelial bladder cancer.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We used microarrays to identify the gene expression changes after SET knockdown in ESCs and 4 day RA differentiated ESCs
Publication Title
Alternative SET/TAFI Promoters Regulate Embryonic Stem Cell Differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We used microarrays to identify the gene expression changes after Smarcd1 knockdown in ESCs and 4 day RA differentiated ESCs
Publication Title
Differential association of chromatin proteins identifies BAF60a/SMARCD1 as a regulator of embryonic stem cell differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We used microarrays to identify the gene expression changes in Cbx1-/- (HP1beta) knockout embryonic stem cells (ESCs) and Cbx5-/- (HP1alpha) knockout ESCs compared to WT ESCs and in embryoid bodies (EBs) differentiated from those three ESC types.
Publication Title
Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples