Filters
Technology
Platform
GSE6283
Homo sapiens
21 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Among full autosomal trisomies, only trisomies of chromosome 21 (Down syndrome, DS), 18 (Edward syndrome, ES) and 13 (Patau syndrome, PS) are compatible with postnatal survival. But the mechanisms, how a supernumerary chromosome disrupts the normal development and causes specific phenotypes, are still not fully explained. As an alternative to gene dosage effects due to the trisomic chromosome, a genome-wide transcriptional dysregulation has been postulated. The aim of this study was to define the transcriptional changes in trisomy 13, 18, and 21 during early fetal development in order to define whether (1) overexpression of genes of the trisomic chromosome contributes solely to the phenotype, if (2) all genes of the trisomic chromosome are upregulated similarly and whether the ratio of gene expression is in agreement with the gene dosis, (3) whether the different trisomies behave similarly in the characteristics of transcriptional dysregulation, and (4) whether transcriptional pattern can be potentially used in prenatal diagnosis. Methods: Using oligonucleotide microarrays (Affymetrix, U133 Plus 2.0), we analyzed whole genome expression profiles representing 54.000 probe sets in cultured amniocytes (AC) and chorion villus cells (CV) from pregnancies with a normal karyotype and with trisomies of human chromosomes 21, 18 and 13. Findings: We observed a low to moderate up-regulation for a subset of genes of the trisomic chromosomes. Transcriptional level of approximately 12-13 % of the supernumerary chromosome appeared similar to the respective chromosome pair in normal karyotypes. Expression values as well as the expression patterns of genes from the trisomic chromosome can distinguish the respective trisomic samples from euploid controls. A subset of chromosome 21-genes including the DSCR1-gene involved in fetal heart development was consistently up-regulated in different tissues (AC, CV) of trisomy 21 fetuses whereas only minor changes were found for genes of all other chromosomes. In contrast, in trisomy 13 and trisomy 18 vigorous downstream transcriptional changes were found. Interpretation: Global transcriptome analysis for autosomal trisomies 13, 18, and 21 supported a combination of the two major hypotheses. As several transcriptional pathways are altered, complex regulatory mechanisms are involved in the pathogenesis of autosomal trisomies. A genome-wide transcriptional dysregulation was predominantly observed in trisomies 13 and 18, whereas a more to chromosome 21 restricted expression alteration was found in trisomy 21.
Publication Title
Specific transcriptional changes in human fetuses with autosomal trisomies.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The C57BL/6.NOD-Aec1Aec2 mouse is a model for primary Sjgrens syndrome and was constructed by introducing two genetic intervals derived from the NOD mouse that confers Sjgrens syndrome (SjS)-like disease in SjS-non-susceptible C57BL/6 mice.
Publication Title
Transcriptional landscapes of emerging autoimmunity: transient aberrations in the targeted tissue's extracellular milieu precede immune responses in Sjögren's syndrome.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Hepatocytes are polarized epithelial cells whose function depends upon their ability to distinguish between the apical and basolateral surfaces that are located at intercellular tight junctions. It has been proposed that the signaling cascades that originate at these junctions influence cellular activity by controlling gene expression in the cell nucleus. To assess the validity of this proposal with regard to hepatocytes, we depleted expression of the tight junction protein junctional adhesion molecule-A (JAM-A) in the HepG2 human hepatocellular carcinoma cell line. Reduction of JAM-A resulted in a striking change in cell morphology, with cells forming single-layered sheets instead of the normal multi-layered clusters. In the absence of JAM-A, other tight junction proteins were mislocalized, and canaliculi, which form the apical face of the hepatocyte, were consequently absent. While most changes in gene expression were modest, there was a strong transcriptional induction of the adherens junction protein E-cadherin in cells with reduced levels of JAM-A. This increase in E-cadherin was partially responsible for the observed alterations in cell morphology and mislocalization of tight junction proteins. We therefore propose that we have uncovered a novel mechanism for crosstalk between specific components of tight and adherens junctions that can be utilized to regulate adhesion between hepatic cells and to maintain hepatocyte cell polarity.
Publication Title
Junctional adhesion molecule-A is critical for the formation of pseudocanaliculi and modulates E-cadherin expression in hepatic cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 28 Downloadable Samples
Illumina HiSeq 2000
Description
The use of alternative polyadenylation sites is common and affects the post-transcriptional fate of mRNA, including its stability, localization, and translation. Here we present a method for genome-wide and strand-specific mapping of poly(A) sites and quantification of RNA levels at unprecedented efficiency by using an on-cluster dark T-fill procedure on the Illumina sequencing platform. Our method outperforms former protocols in quality and throughput, and reveals new insights into polyadenylation in Saccharomyces cerevisiae. Overall design: Experimental benchmark of five different protocols (3tfill, bpmI, internal, rnaseq and yoon) for genome-wide identification of polyadenylation sites in Saccharomyces cerevisiae and transcript quantification. RNA was extracted from WT cells grown in glucose (ypd) or galactose (ypgal) as carbon source. The same RNA was used for 3 independent library constructions (technical replicates, rep).
Publication Title
An efficient method for genome-wide polyadenylation site mapping and RNA quantification.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
We examined the transcriptional changes modulated by estrogen receptor beta (ERß) by performing global transcriptome analysis. U87 cells were transduced with lentiviral particles carrying either empty vector or ERß-FLAG expression vector and the RNA was isolated and utilized for RNA-seq analysis. Our results demonstrated that ERß modulated genes were related to homologous recombination, DNA damage response, ATM signaling and cell cycle pathways. Overall design: Total RNA was isolated from U87 cells expressing either empty vector or ERß expression vector. Illumina TruSeq RNA Sample Preparation was performed following manufacturer's protocol. Samples were run on an Illumina HiSeq 2000 in duplicate. The combined raw reads were aligned to UCSC hg19 and genes were annotated by Tophat2. Genes were annotated and quantified by HTSeq-DESeq pipeline.
Publication Title
Estrogen receptor beta enhances chemotherapy response of GBM cells by down regulating DNA damage response pathways.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Saccharomyces cerevisiae
- 16 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
TORC1 is a structurally and functionally conserved multiprotein complex that regulates many aspects of eukaryote growth including the synthesis and assembly of ribosomes. The protein kinase activity of this complex is responsive to environmental cues and is potently inhibited by the natural product macrolide rapamycin. Insights into how TORC1 regulates growth have been provided with the recent identification of the rapamycin-sensitive phosphoproteome in yeast. Building on these data, we show here that Sch9, an AGC family kinase and direct substrate of TORC1, promotes ribosome biogenesis (ribi) and ribosomal protein (RP) gene expression via direct inhibitory phosphorylation of three transcription repressors, Stb3, Dot6 and Tod6. Dephosphorylation of these factors allows them to recruit the RPD3L histone deactelyase complex to ribi/RP gene promoters. Since rRNA and tRNA transcription are also under its control, Sch9 appears to be well positioned to coordinately regulate transcriptional aspects of ribosome biogenesis. Overall design: mRNA-Seq of 8 S. cerevisiae strains treated with either DMSO alone or 1NM-PP1, a small molecule inhibitor for analog-sensitive kinases such as sch9-as.
Publication Title
Sch9 regulates ribosome biogenesis via Stb3, Dot6 and Tod6 and the histone deacetylase complex RPD3L.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 40 Downloadable Samples
- Illumina HiSeq 2500
Description
We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential. Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation. Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 trimethylation marks imprinting control regions. Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations. Overall design: GMP and MEP were isolated from Runx1+/+-Tg(vav-Cre) and Runx1fl/fl-Tg(vav-Cre) mice as well as Runx1fl/fl-Tg(vav-Cre) XMP, total RNA extracted and sequenced
Publication Title
Runx1 downregulates stem cell and megakaryocytic transcription programs that support niche interactions.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Mammary epithelial cells MCF10A and HER2 overexpressing MCF10A cells were grown on matrigel in the absence or presence of epidermal growth factor. Cells were lysed and RNA was collected at 1.5,3,5,7,9 days.
Publication Title
Modeling ductal carcinoma in situ: a HER2-Notch3 collaboration enables luminal filling.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Ankrd11 is a potential chromatin regulator implicated in neural development and autism spectrum disorder (ASD) with no known function in the brain. Here, we show that knockdown of Ankrd11 in developing murine or human cortical neural precursors caused decreased proliferation, reduced neurogenesis, and aberrant neuronal positioning. Similar cellular phenotypes and aberrant ASD-like behaviors were observed in Yoda mice carrying a point mutation in the Ankrd11 HDAC-binding domain. Consistent with a role for Ankrd11 in histone acetylation, Ankrd11 was associated with chromatin, colocalized with HDAC3, and expression and histone acetylation of Ankrd11 target genes were altered in Yoda neural precursors. Moreover, the Ankrd11 knockdown-mediated decrease in precursor proliferation was rescued by inhibiting histone acetyltransferase activity or expressing HDAC3. Thus, Ankrd11 is a crucial epigenetic regulator of neural development that controls histone acetylation and gene expression, thereby providing a likely explanation for its association with cognitive dysfunction and ASD.
Publication Title
Ankrd11 is a chromatin regulator involved in autism that is essential for neural development.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
We examined the transcriptional chagnes modulated by ECBI-11 by perfroming global transcriptome analysis. ZR75 cells were treated with either control or ECBI-11 in the presence of E2 for 48 h and the isolated RNA was utilized for RNA-seq analysis. Our results demonstrated that ECBI modulated several genes that are involved in cell cycle, breast cancer signaling, estrogen signaling and apoptosis. Overall design: Total RNA was isolated from the ZR75 cells that were treated with vehicle or ECBI for 48 h. Illumina TruSeq RNA Sample Preparation was performed following manufacturer''s protocol. Samples were run on an Illumina HiSeq 2000 in duplicate. The combined raw reads were aligned to UCSC hg19 and genes were annotated by Tophat. Genes were annotated and quantified by HTSeq-DESeq pipeline.
Publication Title
Estrogen receptor coregulator binding modulators (ERXs) effectively target estrogen receptor positive human breast cancers.
Sample Metadata Fields
No sample metadata fields
View Samples