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SRP151738
Homo sapiens
20 Downloadable Samples
Illumina HiSeq 2500
Description
Background and aims: Despite proven clinical efficacy of vedolizumab (VDZ) for inducing and maintaining remission in patients with Crohn's disease (CD) and ulcerative colitis (UC), subgroups of patients have no therapeutic benefit from anti-a4ß7 integrin therapy with VDZ. Within this study, we aimed to identify genetic, cellular and immunological mechanisms that define response and failure to VDZ treatment.Methods: Intestinal RNA Sequencing was performed in UC and CD patients before and at week 14 of VDZ therapy. a4ß7 expression on peripheral and mucosal immune cells was assessed by flow cytometry and immunohistochemistry. Cellular modes of VDZ mediated action were analysed ex vivo and in VDZ treated IBD patients.Results: Transcriptome analysis showed an impairment of signaling cascades associated with adhesion, diapedesis and migration of granulocytes and agranulocytes upon VDZ therapy. In non-remitters to VDZ therapy, a tissue destructive and leucocyte mediated inflammatory activity with activation of TNF dependent pathways was present, all of which were inhibited in remitters to VDZ. Clinical remission was associated with a significant reduction of a4ß7 expression on Th2 and Th17 polarized mucosal CD4+ T cells at week 14 of VDZ therapy and with significantly higher numbers of a4ß7 expressing mucosal cells prior to the initiation of VDZ therapy compared to non-remitters.Conclusions: Intestinal a4ß7 expression prior to VDZ therapy might represent a biomarker that predicts therapeutic response to subsequent VDZ treatment. Due to high activation of TNF signaling in VDZ non-remitters, anti-TNF treatment might represent a promising therapeutic strategy in VDZ refractory patients.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part, Disease, Treatment, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Our aim was to identify genes that were differentially expressed in microglia stimulated with Lipopolysaccharide, Luteolin, or both.
Publication Title
Luteolin triggers global changes in the microglial transcriptome leading to a unique anti-inflammatory and neuroprotective phenotype.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
PU.1 is a key transcription factor for macrophage differentiation. Novel PU.1 target genes were identified by mRNA profiling of PU.1-deficient progenitor cells (PUER) before and after PU.1 activation. We used two different types of Affymetrix DNA-microarrays (430 2.0 arrays and ST 1.0 exon arrays) to characterize the global PU.1-regulated transcriptional program underlying the early processes of macrophage differentiation.
Publication Title
Transcriptomic profiling identifies a PU.1 regulatory network in macrophages.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
To define the genes and pathways which are influenced by Foxp1 in the striatum at embryonic stage (E)18.5 we performed a microarray expression study comparing gene expression in striatal tissue from WT and Nestin-Cre (Foxp1-/-) animals.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The pre-synaptic protein -synuclein is a key player in the pathogenesis of Parkinson's disease. Together with accumulation and missfolding of -synuclein protofibrils serve as seed structures for the aggregation of numerous proteins in the cytoplasm of neuronal cells, the so-called Lewy bodies. Furthermore, missense mutations in the SNCA gene and gene multiplications lead to autosomal dominant forms of familiar PD. However, so far the exact biological role of -synuclein in normal brain is elusive. To gain more insights into the biological function of this protein we monitored whole genome expression changes in dopaminergic neuroblastoma cells (SH-SY5Y) caused by a 90% reduction of -synuclein by RNA interference.
Publication Title
Microarray expression analysis of human dopaminergic neuroblastoma cells after RNA interference of SNCA--a key player in the pathogenesis of Parkinson's disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pigment Epithelium-Derived Factor (PEDF) has recently been identified as a factor that is significantly upregulated in late-stage osteoarthritic cartilage in which chondrocytes are confronted with terminal differentiation and cell death. Since PEDF is known to induce cell death of endothelial cells, it may also be responsible for terminal differentiation and cell death in cartilage.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The hearts rhythm is initiated and regulated by a group of specialized cells in the sinoatrial node (SAN), the primary pacemaker of the heart. Abnormalities in the development of the SAN can result in irregular heart rates (arrhythmias). Although several of the critical genes important for SAN formation have been identified, our understanding of the transcriptional network controlling SAN development remains at a relatively early stage. The homeodomain transcription factor Shox2 plays an essential early role in the specification and patterning of the SAN.
Publication Title
Islet1 is a direct transcriptional target of the homeodomain transcription factor Shox2 and rescues the Shox2-mediated bradycardia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Newcastle disease virus (NDV) is an avian virus that selectively replicates and kills many different types of cancer cells and is being developed for cancer treatment. Our aim was to establish persistent infection in EJ28 and TCCSUP bladder cancer cells and identify the dysregulated genes and disrupted molecular pathways associated with persistent infection.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
- Ion Torrent Proton
Description
The RNA-Seq experiment was performed to test whether loss of CHD7 does not affect the expression of DNA double-strand break repair proteins.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Cell differentiation is based on a synchronised orchestra of complex pathways of intrinsic and extrinsic signals that manifest in the induced expression of specific transcription factors and pivotal genes within the nucleus. One cannot ignore the epigenetic status of differentiating cells, comprising not only histones and DNA modifications but also the spatial and temporal intranuclear chromatin organisation, which is an important regulator of nuclear processes. In the present study, we investigated the nuclear architecture of human primary myoblasts and myocytes in an in vitro culture, with reference to global changes in genomic expression. Repositioning of the chromosomal centromeres, along with alterations in the nuclear shape and volume, was observed as a consequence of myotube formation. Moreover, the microarray data showed that during in vitro myogenesis cells tend to silence rather than induce gene expression. The creation of a chromosome map marked with gene expression changes that were at least 2-fold confirmed the observation. Additionally, almost all of the chromosomal centromeres in the differentiated cells preferentially localised near the nuclear periphery when compared to the undifferentiated cells. The exceptions were chromosomes 7 and 11, in which we were unable to confirm the centromere repositioning.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples