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GSE12407
Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Human mononuclear cells were cultured in 2 phases. In the 1st phase the culture medium contained cyclosporine A the 2nd phase contained SCF and erythropoietin. Cells were collected at 3 stages of differentiation; on day 6, 10, 12 and represented early erythroblasts, medium stage and normoblasts.
Publication Title
Identification of gene networks associated with erythroid differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 91 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. We sought to elucidate the molecular mechanisms underlying the clinical efficacy of tofacitinib in patients with psoriasis. Twelve patients with plaque psoriasis were randomized (3:1) to receive 10mg of tofacitinib or placebo twice daily for 12weeks. Biopsy specimens were taken from nonlesional (baseline) and lesional (baseline, days 1 and 3, and weeks 1, 2, 4, and 12) skin. Biopsy specimens were examined for psoriatic epidermal features (thickness, Ki67+ keratinocytes and keratin 16 [KRT16] mRNA expression, and phosphorylated signal transducer and activator of transcription [pSTAT]+ nuclei) and T-cell and dendritic cell (DC) subsets by using immunohistochemistry, and mRNA transcripts were quantified by using a microarray. In lesional skin keratinocyte pSTAT1 and pSTAT3 staining was increased at baseline but reduced after 1day of tofacitinib (baseline, median of 1290 pSTAT1+ cells/?m2; day 1, median of 332 pSTAT1+ cells/?m2; and nonlesional, median of 155 pSTAT1+ cells/?m2). Epidermal thickness and KRT16 mRNA expression were significantly and progressively reduced after days 1 and 3 of tofacitinib administration, respectively (eg, KRT16 decreased 2.74-fold, day 3 vs baseline, P=.016). Decreases in DC and T-cell numbers were observed after weeks 1 and 2, respectively. At week 4, significant decreases in IL-23/TH17 pathways were observed that persisted through week 12. Improvements in clinical and histologic features were strongly associated with changes in expression of psoriasis-related genes and reduction in IL-17 gene expression. Tofacitinib has a multitiered response in patients with psoriasis: (1) rapid attenuation of keratinocyte Janus kinase/STAT signaling; (2) removal of keratinocyte-induced cytokine signaling, leading to reductions in pathologic DC andT-cell numbers to nonlesional levels; and (3) inhibition of the IL-23/TH17 pathway.
Publication Title
Tofacitinib attenuates pathologic immune pathways in patients with psoriasis: A randomized phase 2 study.
Sample Metadata Fields
Specimen part, Disease, Treatment, Subject, Time
View Samples- Mus musculus
- 17 Downloadable Samples
Illumina HiSeq 2500
Description
We show that mesenchymal CSC-like cells express an embryonic stem cell signature that is mutant p53 dependent Overall design: Examination of three p53 mutant mesenchymal stem cells and ten derived CSC-like cell lines and 2 derived p53 mutant KO clones compared to control clones
Publication Title
A Mutant p53-Dependent Embryonic Stem Cell Gene Signature Is Associated with Augmented Tumorigenesis of Stem Cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Drosophila melanogaster
- 19 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We profiled the transcriptome of Drosophila melanogaster embryos in ttk2D50 embryos or after over-expression using btl-GAL4; UAS-ttk, respectively. We further isolated cells that express btl-enh-RFPmoe (Cabernard and Affolter 2005) and FACS sorting, and profiled their transcriptomes in the same genetic backgrounds.
Publication Title
Tramtrack is genetically upstream of genes controlling tracheal tube size in Drosophila.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In order to obtain a global picture regarding regulation of p53 in liver cells we used HepG2 hepatoma cells.We created two isogenic sub-cultures of HepG2 cells with altered expression of p53.
Publication Title
Chemotherapeutic agents induce the expression and activity of their clearing enzyme CYP3A4 by activating p53.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- IlluminaGenomeAnalyzerIIx
Description
Monocytes are a heterogeneous cell population with subset-specific functions and phenotypes. The differential expression of CD14 and CD16 distinguishes classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes. However, CD14++CD16+ monocytes remain the most poorly characterized subset so far. Therefore we analyzed the transcriptomes of the three monocyte subsets using SuperSAGE in combination with high-throughput sequencing. Analysis of 5,487,603 tags revealed unique identifiers of CD14++CD16+ monocytes, delineating these cells from the two other monocyte subsets. CD14++CD16+ monocytes were linked to antigen processing and presentation (e.g. CD74, HLA-DR, IFI30, CTSB), to inflammation and monocyte activation (e.g. TGFB1, AIF1, PTPN6), and to angiogenesis (e.g. TIE2, CD105). Therefore we provide genetic evidence for a distinct role of CD14++CD16+ monocytes in human immunity. Overall design: Human monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) were isolated from 12 healthy volunteers based on MACS technology. Total RNA from monocyte subsets was isolated and same aliquots from each donor and monocyte subset were matched for SuperSAGE. Three SuperSAGE libraries (CD14++CD16-, CD14++CD16+ and CD14+CD16++) were generated.
Publication Title
SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset.
Sample Metadata Fields
No sample metadata fields
View Samples- Staphylococcus aureus
- 37 Downloadable Samples
- Affymetrix S. aureus Genome Array (saureus)
Description
Staphylococcus aureus is a highly adaptable human pathogen; therefore a constant search for new effective antibiotic compounds is being preformed. Gene expression profiling can be used to determine potential targets and mechanisms of action (MOA) of known or potential drugs. The goal of our study was a development of a focused transcriptome platform to be used for confirming the MOA of new chemical entities which are designed as inhibitors of Mur ligases. A model transcriptional profile was set up for well described inhibitor of MurA ligase, fosfomycin. Moreover, we wanted to identify the pathways and processes primarily affected by this compound. S. aureus ATCC 29213 cells were treated with low concentrations of fosfomycin (1 and 4 g/ml, respectively) and harvested at 10, 20 and 40 minutes after treatment, respectively. RNA was isolated, transcribed, labeled and hybridized to S. aureus GeneChips, representing approximately 3000 S. aureus genes.
Publication Title
Revealing fosfomycin primary effect on Staphylococcus aureus transcriptome: modulation of cell envelope biosynthesis and phosphoenolpyruvate induced starvation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
E47 represses Foxp3 transcription, albeit indirectly through the activation of unknown negative regulatory of Foxp3 transcription.
Publication Title
Id3 Maintains Foxp3 Expression in Regulatory T Cells by Controlling a Transcriptional Network of E47, Spi-B, and SOCS3.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 162 Downloadable Samples
- Illumina HiSeq 2500
Description
Toolsets available for in-depth analysis of scRNAseq datasets by biologists with little informatics experience is limited. Here we describe an informatics tool (PyMINEr) that fully automates cell type identification, cell type-specific pathway analyses, graph theory-based analysis of gene regulation, and detection of autocrine/paracrine signaling networks in silico. We applied PyMINEr to interrogate human pancreatic islet scRNAseq datasets and discovered several features of co-expression graphs including: concordance of scRNAseq-graph structure with both protein-protein interactions and 3D-genomic architecture; association of high connectivity and low expression genes with cell type-enrichment; and potential for graph-structure to clarify potential etiologies of enigmatic disease-associated variants. We further created a consensus co-expression network and autocrine/paracrine signaling networks within and across islet cell types from 7-datasets. PyMINEr correctly identified changes in BMP/WNT signaling associated with cystic fibrosis pancreatic acinar-cell loss. This proof-of-principle study demonstrates that the PyMINEr framework will be a valuable resource for scRNAseq analyses. Overall design: Human islets were obtained from the integrated islet distribution program (IIDP), cultured overnight, then prepared for scRNAseq via the Fluidigm C1 platform. RNAseq was perfromed on Illumina HiSeq 2500.
Publication Title
PyMINEr Finds Gene and Autocrine-Paracrine Networks from Human Islet scRNA-Seq.
Sample Metadata Fields
Sex, Age, Specimen part, Race, Subject
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Duplication of chromosomal arm 20q occurs in prostate, cervical, colon, gastric, bladder, melanoma, pancreas and breast cancer, suggesting that 20q amplification may play a key causal role in tumorigenesis. According to an alternative view, chromosomal instabilities are mainly a common side effect of cancer progression. To test whether a specific genomic aberration might serve as a cancer initiating event, we established an in vitro system that models the evolutionary process of early stages of prostate tumor formation; normal prostate cells were immortalized and cultured for 650 days till several transformation hallmarks were observed. Gene expression patterns were measured and chromosomal aberrations were monitored by spectral karyotype analysis at different times. Several chromosomal aberrations, in particular duplication of chromosomal arm 20q, occurred early in the process and were fixed in the cell populations, while other aberrations became extinct shortly after their appearance. A wide range of bioinformatic tools, applied to our data and to data from several cancer databases, revealed that spontaneous 20q amplification can promote cancer initiation. Our computational model suggests that deregulation of some key pathways, such as MAPK, p53, cell cycle regulation and Polycomb group factors, in addition to activation of several genes like Myc, AML, B-Catenin and the ETS family transcription factors, are key steps in cancer development driven by 20q amplification. Finally we identified 13 cancer initiating genes, located on 20q13, which were significantly overexpressed in many tumors, with expression levels correlated with tumor grade and outcome; these probably play key roles in inducing malignancy via20q amplification.
Publication Title
Amplification of the 20q chromosomal arm occurs early in tumorigenic transformation and may initiate cancer.
Sample Metadata Fields
Specimen part
View Samples