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Mus musculus
12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Much is known concerning the cellular and molecular basis for CD8+ T memory immune responses. Nevertheless, conditions that selectively support memory generation have remained elusive. Here we show that an immunization regimen that delivers TCR signals through a defined antigenic peptide, inflammatory signals through LPS, and growth and differentiation signals through the IL-2R initially favors antigen-specific CD8+ T cells to rapidly and substantially develop into tissue-residing T effector-memory cells by TCR transgenic OVA-specific OT-I CD8+ T cells. Amplified CD8+ T memory development depends upon a critical frequency of antigen-specific T cells and direct responsiveness to IL-2. A homologous prime-boost immunization protocol with transiently enhanced IL-2R signaling in normal mice led to persistent polyclonal antigen-specific CD8+ T cells that supported protective immunity to Listeria monocytogenes. These results identify a general approach for amplified T memory development that may be useful to optimize vaccines aimed at generating robust cell-mediated immunity.
Publication Title
Transient enhanced IL-2R signaling early during priming rapidly amplifies development of functional CD8+ T effector-memory cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene expression profiles from the aortic arch of Ldlr-/-Apob100/100 Mttpflox/flox Mx1-Cre mice at different stages of atherosclerosis development
Publication Title
Transcriptional profiling uncovers a network of cholesterol-responsive atherosclerosis target genes.
Sample Metadata Fields
Age, Specimen part
View Samples- Rattus norvegicus
- 28 Downloadable Samples
- Affymetrix Rat Gene 1.1 ST Array (ragene11st)
Description
Objective: Shear forces play a key role in the maintenance of vessel wall integrity. Current understanding regarding shear-dependent gene expression is mainly based on in vitro or in vivo observations with experimentally deranged shear, hence reflecting acute molecular events in relation to flow. Our objective was to combine computational fluid dynamic (CFD) simulations with global microarray analysis to study flow-dependent vessel wall biology in portions of the entire aorta under physiological conditions. Methods and Results: Animal-specific WSS magnitude and vector direction were estimated using CFD based on aortic geometry and flow information acquired by MRI. Two distinct flow pattern regions were identified in the normal rat aorta; the distal part of the inner curvature being exposed to low WSS and a non-uniform vector direction, and a region along the outer curvature being subjected to markedly higher levels of WSS and a uniform vector direction. Microarray analysis identified numerous novel mechanosensitive genes, including Hand2, trpc4 and slain2, and confirmed well-known ones, such as klf2 and BMP4. Three genes were further validated for protein , including Hand2, which showed higher expression in the endothelium in regions exposed to disturbed flow. Gene ontology analysis revealed an over-representation of genes involved in transcriptional regulation.
Publication Title
Characterization of shear-sensitive genes in the normal rat aorta identifies Hand2 as a major flow-responsive transcription factor.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
IlluminaHiSeq2500
Description
High uniform fluid shear stress (FSS) is atheroprotective and preserves the endothelial phenotype and function through activation of downstream mediators such as MAPK7 (Erk5). Endothelial cells respond to FSS thanks to mechanotransduction. However, how the resulting signaling is integrated and resolved at the epigenetic level, remains elusive. We hypothesized that Polycomb methyltransferase EZH2 is involved in the effects of FSS in human endothelial cells. We showed that FSS decreases the expression of the Polycomb methyltransferase EZH2. Despite simultaneous activation of MAPK7, MAPK7 pathway does not directly influence the transcription of EZH2. Interestingly though, the knock down of EZH2 activates the protective MAPK7 signaling in endothelial cells, even in the absence of FSS. To understand the influence of the FSS-decreased expression of EZH2 on endothelial transcriptome, we performed RNA-seq and differential gene expression analysis. We identified candidate groups of genes dependent on both EZH2 and FSS. Among those, Gene Ontology overrepresentation analysis revealed highly significant enrichment of the cell cycle-related genes, suggesting changes in proliferation. Indeed, the depletion of EZH2 strongly inhibited endothelial proliferation, indicating cell cycle arrest. The concomitant decrease in CCNA expression suggests the transition of endothelial cells into a quiescent phenotype. Further bioinformatical analysis suggested TXNIP as a possible mediator between EZH2 and cell cycle-related gene network. Our data show that EZH2 is a FSS-responsive gene. Decreased EZH2 levels enhance the activation of the atheroprotective MAPK7 signaling. Decrease in EZH2 under FSS mediates the decrease in the expression of the network of cell cycle-related genes, which allows the cells to enter quiescence. EZH2 is therefore important for the protective effects of FSS in endothelium. Overall design: Puromycin-selected HUVEC (Human Umbilical Vein Endothelial Cells, Lonza, Switzerland) cells, expressing either scrambled control (SCR) or anti-EZH2 short-hairpin (shEZH2) constructs (at total 7 days after the first viral transduction), were used in FSS experiments (72h of control static culture or exposure to 20 dynes/cm2 of fluid shear stress, using Ibidi pump system (in µ-Slides I 0.4 Luer, Ibidi, Planegg/Martinsried, Germany)). Each replicate experiment consisted of viral transductions and puromycin selection of a separate HUVEC batch, followed by the FSS experiment. Two FSS experimental sets of the same HUVEC batch were run every time in parallel and lysed at the same end time point, one in RNAse-free conditions with RNA-Easy Mini Plus kit RLT Plus lysis buffer (QIAGEN, Venlo, The Netherlands), and one with RIPA buffer. The RIPA-lysates were analyzed with Western blotting and confirmed the complete (no protein present) knock-down of EZH2. From the RNA-lysates, RNA was isolated using the RNA-Easy Mini Plus kit (QIAGEN, Venlo, The Netherlands). High quality RNA samples (pre-assessed by Nanodrop measurements) were further processed in the Genome Analysis Facility of the University Medical Center Groningen. The RNA quality and integrity were verified using PerkinElmer Labchip GX with a cut-off value of 9 (scale 1 to 10, where 9 is very high quality RNA). RNA library was created in accordance with the TruSeqTM RNA Sample Preparation v2 Guide (Illumina, San Diego, CA, USA), using the PerkinElmer Sciclone liquid handler, resulting in 330bp cDNA fragments. The paired-end sequencing (100bp reads) was performed using the Illumina HiSeqTM 2500. (Quoted from the Materials and Methods of the related manuscript, with adjustments).
Publication Title
The decrease in histone methyltransferase EZH2 in response to fluid shear stress alters endothelial gene expression and promotes quiescence.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This study determined the genes that are differentially expressed when regulatory T cells (Tregs) were isolated from the lamina propria of the small and large intestine from mice with impaired IL-2R signaling (designated Y3) or impaired IL-2R signaling and lack of CD103 expression (designated Y3/CD103-/-) when compared to Tregs from WT mice. 204 unique annotated mRNAs were differentially expressed by 1.5 fold between these 3 groups (Fig. 6B). Very few mRNAs were uniquely up or down regulated in relationship to impaired IL-2R signaling or the combination of impaired IL-2R signaling and lack of CD103 expression. Thus, lack of CD103 does not obviously regulated signaling in Tregs in the gut mucosa and most differentially expressed genes were due to impaired IL_2R signaling. Gene enrichment analysis of these differentially expressed genes identified 4 major enrichment groups (EG) are: EG1, Cytokine-cytokine receptor interaction and the JAK-STAT signaling pathway; EG2, regulation of lymphocyte activation and proliferation; EG3, regulation of cell death and the caspase pathway in apoptosis; and EG4, transcription.
Publication Title
IL-2Rβ-dependent signaling and CD103 functionally cooperate to maintain tolerance in the gut mucosa.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 54 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
AoSMC and FB were cultured and exposed to transforming growth factor beta1 (TGFb1) prior to the exon array analysis
Publication Title
Aneurysm development in patients with a bicuspid aortic valve is not associated with transforming growth factor-β activation.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples
GSE36527- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Thymic-derived natural T regulatory cells (nTregs) are characterized by functional and phenotypic heterogeneity. Recently, a small fraction of peripheral Tregs have been shown to express Klrg1, but it remains unclear the extent Klrg1 defines a unique Treg subset. Here we show that Klrg1+ Tregs represent a terminally differentiated Treg subset derived from Klrg1- Tregs. This subset is a recent antigen-responsive and a highly activated short-lived Treg population that expresses enhanced levels of Treg suppressive molecules and that preferentially resides within mucosal tissues. The development of Klrg1+ Tregs also requires extensive IL-2R signaling. This activity represents a distinct function for IL-2, independent from its contribution to Treg homeostasis and competitive fitness. These and other properties are analogous to terminally differentiated short-lived CD8+ T effector cells. Our findings suggest that an important pathway driving antigen-activated conventional T lymphocytes also operates for Tregs.
Publication Title
IL-2 receptor signaling is essential for the development of Klrg1+ terminally differentiated T regulatory cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
We report that decreased expression and activity of AhR exacerbates murine neovascular age-related macular degeneration, and increases cell migration and tube formation. The mechanism involves increased expression of pro-angiogenic mediators and altered matrix degradation. The results of our study suggest that the AhR signaling pathway may be important in multiple AMD related pathways. Overall design: Gene expression analysis in the retinal pigment epithelium (RPE)-choroid tissue from AhR knockout mice contrasted against wild-type age-matched controls.
Publication Title
Aryl hydrocarbon receptor knock-out exacerbates choroidal neovascularization via multiple pathogenic pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 8 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
The objective of the present study is to investigate if females have the ability to recognise X or Y chromosome bearing spermatozoa and present a different response to different spermatozoa.
Publication Title
The battle of the sexes starts in the oviduct: modulation of oviductal transcriptome by X and Y-bearing spermatozoa.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Chronic lymphocytic leukemia (CLL) is a biologically heterogeneous illness with a variable clinical course. Loss of chromosomal material on chromosome 13 at cytoband 13q14 is the most frequent genetic abnormality in CLL, but the molecular aberrations underlying del13q14 in CLL remain incompletely characterized. We analyzed 171 CLL cases for LOH and sub-chromosomal copy loss on chromosome 13 in DNA from FACS-sorted CD19+ cells and paired buccal cells using the Affymetrix XbaI 50K SNP-array platform. The resulting high-resolution genomic maps, together with array-based measurements of expression levels of RNA in CLL cases with and without del13q14 and Q-PCR-based expression analysis of selected genes support the following conclusions: i) del13q14 is heterogeneous and composed of multiple subtypes with deletion of Rb or the miR15a/16 loci serving as anatomic landmarks, respectively ii) del13q14 type Ia deletions are relatively uniform in length and extend from breakpoints close to the miR15a/16 cluster to a newly identified telomeric breakpoint cluster at ~50.2-50.5 Mb physical position iii) LATS2 RNA levels are ~2.6-2.8-fold lower in cases with del13q14 type I that do not delete Rb as opposed to all other CLL cases and iv) ~15% of CLL cases display marked reductions in miR15a/16 expression often but not invariably associated with bi-allelic miR15a/16 loss. This data should aid future investigations into biological differences imparted on CLL by different del13q14 subtypes including investigations into LATS2 as one of the genes found deregulated as part of del13q14.
Publication Title
Integrated genomic profiling of chronic lymphocytic leukemia identifies subtypes of deletion 13q14.
Sample Metadata Fields
No sample metadata fields
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