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GSE35844
Mus musculus
9 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
MiRNAs have the potential to regulate cellular differentiation programs. However, miRNA-deficiency in primary hematopoietic stem cells (HSCs) results in HSC depletion in mice, leaving the question of whether miRNAs play a role in early-lineage decisions unanswered. To address this issue, we deleted Dicer1, which encodes an essential RNaseIII enzyme for miRNA biogenesis, in murine CCAAT/enhancer-binding protein alpha (C/EBPA)-positive myeloid-committed progenitors in vivo. In contrast to the results in HSCs, we found that miRNA depletion affected neither the number of myeloid progenitors nor the percentage of C/EBPA-positive progenitor cells. Analysis of gene-expression profiles from wild type and Dicer1-deficient granulocyte-macrophage progenitors (GMPs) revealed that 20 miRNA families were active in GMPs. Of the derepressed miRNA targets in Dicer1-null GMPs, 27% are normally exclusively expressed in HSCs or are specific for multi-potent progenitors and erythropoiesis, indicating an altered gene-expression landscape. Dicer1-deficient GMPs were defective in myeloid development in vitro and exhibited an increased replating capacity, indicating a regained self-renewal potential of these cells. In mice, Dicer1 deletion blocked monocytic differentiation, depleted macrophages and caused myeloid dysplasia with morphological features of Pelger-Hut anomaly. These results provide evidence for a miRNA-controlled switch for a cellular program of self-renewal and expansion towards myeloid differentiation in GMPs.
Publication Title
Dicer1 deletion in myeloid-committed progenitors causes neutrophil dysplasia and blocks macrophage/dendritic cell development in mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A key requisite for the success of a dendritic cell (DC)-based vaccine in treating malignancies is the capacity of the DCs to attract immune effector cells for further interaction and activation, considering crosstalk with DCs is partially regulated by cell-contact-dependent mechanisms. Although critical for therapeutic efficacy, immune cell recruitment is a largely overlooked aspect regarding optimization of DC therapy. In this paper we examine if the so-called interleukin (IL)-15 DC vaccine provides a favorable chemokine milieu for recruiting T cells, natural killer (NK) cells and gamma delta () T cells, in comparison with the IL-4 DCs used routinely for clinical studies, as well as the underlying mechanisms of immune cell attraction by IL-15 DCs. Chemokine signaling is studied both at the RNA level, using microarray data of mature DCs, and functional level, by means of a transwell chemotaxis assay. Important to note, the classic IL-4 DC vaccine falls short to attract the required immune effector lymphocytes, whereas the IL-15 DCs provide a favorable chemokine milieu for recruiting all cytolytic effector cells. The elevated secretion of the chemokine (C-C motif) ligand 4 (CCL4), also known as macrophage inflammatory protein-1 (MIP-1), by IL-15 DCs underlies the enhanced migratory responsiveness of T cells, NK cells and T cells. Namely, neutralizing its receptor CCR5 resulted in a significant drop in migration of the aforementioned effector cells towards IL-15 DCs. These findings should be kept in mind in the design of future DC-based cancer vaccines.
Publication Title
Desirable cytolytic immune effector cell recruitment by interleukin-15 dendritic cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
To obtain insight in the genome-wide response of heterologous carotenoid production in Saccharomyces cerevisiae, we have analyzed the transcriptome of S. cerevisiae strains overexpressing carotenogenic genes from the yeast Xanthophyllomyces dendrorhous. For this purpose, two strains producing different levels of carotenoids were grown in carbon-limited continuous cultures and genome-wide expression was analyzed. The strain producing low carotenoid levels did not exhibit a clear genome-wide transcriptional response, suggesting that low carotenoid levels do not result in cellular stress. Transcriptome analysis of a strain producing high carotenoid levels resulted in specific induction of genes involved in pleiotropic drug resistance (PDR). These genes encode ATP-binding cassette (ABC) type transporters and major facilitator transporters which are involved in secretion of toxic compounds out of cells. Our results suggest that production of high amounts of carotenoids in S. cerevisiae lead to toxicity and that these cells are prone to secrete carotenoids out of the cell. Indeed, secretion of beta-carotene into sunflower oil was observed upon addition of this hydrophobic solvent to the growth medium. Finally, it was observed that deletion of the ABC transporter pdr10, one of the induced PDR transporters, highly decreased the transformation efficiency of an episomal vector containing carotenogenic genes. The few colored transformants that were obtained had decreased growth rates and lower carotenoid production levels compared to control strains transformed with the same carotenogenic genes. These results indicate that Pdr10 might be specifically involved in carotenoid tolerance in S. cerevisiae strains.
Publication Title
Heterologous carotenoid production in Saccharomyces cerevisiae induces the pleiotropic drug resistance stress response.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Knee joint synovium was used for gene expression analysis of mouse collagen induced arthritis (CIA). Synovium was prepared at day 30 after initial sensitization from: healthy controls, CIA animals with no, with mild, with moderate, or with severe joint inflammation. Each sample group is represented by three replicates, each consisting of tissue collected from three to four animals.
Publication Title
Computational design and application of endogenous promoters for transcriptionally targeted gene therapy for rheumatoid arthritis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Synovial biopsies were obtained from rheumatoid arthritis (RA) synovium and from subjects without a joint disease to find gene upregulated during RA.
Publication Title
Disease-Regulated Gene Therapy with Anti-Inflammatory Interleukin-10 Under the Control of the CXCL10 Promoter for the Treatment of Rheumatoid Arthritis.
Sample Metadata Fields
Disease, Disease stage
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
These arrays contain data from the livers of 10 week old L-Pex5 -/- male mice
Publication Title
Carbohydrate metabolism is perturbed in peroxisome-deficient hepatocytes due to mitochondrial dysfunction, AMP-activated protein kinase (AMPK) activation, and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) suppression.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Purpose: To chart the human myometrial transcriptomes before and after the onset of labour. Methods: Tophat splice junction mapping of paired-end reads, HTSeq to generate counts, cufflinks to track transcripts, DESeq, edgeR and baySeq to detect differentially expressed genes and principal component analysis for clustering analyses. Results: We mapped on average 14 million paired-end reads per sample (counting each end individually) to the human genome (build hg19) and covered the expressed transcriptome about 13 times with a TopHat-HTSeq workflow. We performed a comparative analysis with an analogous microarray study (Mittal et al., 2010) and found some overlap between the RNA-seq and the microarray data. Conclusions: Our study is the first RNA-seq study of the human myometrium before and after the onset of labour. We show that while microarray and RNA-seq studies may complement each other, RNA-seq has a much greater resolution. Overall design: At term with and at term without labour human myometrial mRNA profiles were generated by deep sequencing, using Illumina GAIIx (five biological replicates each).
Publication Title
Reconstruction of Cell Surface Densities of Ion Pumps, Exchangers, and Channels from mRNA Expression, Conductance Kinetics, Whole-Cell Calcium, and Current-Clamp Voltage Recordings, with an Application to Human Uterine Smooth Muscle Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 1117 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Whole blood transcriptome analysis in amyotrophic lateral sclerosis: A biomarker study.
Sample Metadata Fields
Sex, Disease
View Samples- Homo sapiens
- 741 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Transcriptome-wide analysis of whole blood gene expression profiles of ALS patients, gender- and age-matched controls and patients diagnosed with diseases mimicking ALS at a tertiary referral center for motor neuron diseases.
Publication Title
Whole blood transcriptome analysis in amyotrophic lateral sclerosis: A biomarker study.
Sample Metadata Fields
Sex, Disease
View Samples- Homo sapiens
- 376 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Transcriptome-wide analysis of whole blood gene expression profiles of ALS patients, gender- and age-matched controls and patients diagnosed with diseases mimicking ALS at a tertiary referral center for motor neuron diseases.
Publication Title
Whole blood transcriptome analysis in amyotrophic lateral sclerosis: A biomarker study.
Sample Metadata Fields
Sex, Disease
View Samples