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GSE57479
Homo sapiens
18 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
It is known that natural killer (NK) cells are a heterogeneous population of functionally distinct NK cell subsets. Here we report on different genomic, phenotypic and functional properties of human NK cell subsets derived from peripheral blood, thymus and bone marrow. NK cell subpopulations were defined via expression of CD56 and CD16.
Publication Title
Specific phenotype and function of CD56-expressing innate immune cell subsets in human thymus.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We compared the aorta of 6-weeks-old mice (young) with 18-months-old mice (old). Using the publicly available tools Sylamer and DIANA-mirExTra, we identified an enrichment for miR-29 binding sites in the 3'UTR of genes downregulated in the aged aortas. We subsequently showed that inhibition of miR-29 in aged mice prevented dilation of the aorta.
Publication Title
MicroRNA-29 in aortic dilation: implications for aneurysm formation.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We compared the heart of 6-weeks-old mice (young) with 18-months-old mice (old)
Publication Title
MicroRNA-34a regulates cardiac ageing and function.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
MicroRNAs are endogenously expressed small non-coding RNAs that regulate gene expression on the posttranscriptional level. The miR-17-92 cluster (encoding miR-17, -18a, -19a/b, -20a and miR-92a) is highly expressed in tumor cells and is up-regulated by ischemia. Whereas miR-92a was recently identified as negative regulator of angiogenesis, the specific functions of the other members of the cluster are less clear. Here we demonstrate that overexpression of miR-17, -18a, -19a and -20a significantly inhibited 3D spheroid sprouting in vitro, whereas inhibition of miR-17, -18a and -20a augmented endothelial cell (EC) sprout formation. Inhibition of miR-17 and miR-20a in vivo using antagomirs significantly increased the number of perfused vessels in matrigel plugs, whereas antagomirs, that specifically target miR-18a and miR-19a were less effective. However, systemic inhibition of miR-17/20 did not affect tumor angiogenesis. Further mechanistic studies showed that miR-17/20 targets several pro-angiogenic genes. Specifically, Janus kinase 1 (Jak1) was shown to be a direct target of miR-17. In summary, we show that miR-17/20 exhibit a cell intrinsic anti-angiogenic activity in ECs. Inhibition of miR-17/20 specifically augmented neovascularization of matrigel plugs, but did not affect tumor angiogenesis indicating a context-dependent regulation of angiogenesis by miR-17/20 in vivo.
Publication Title
Members of the microRNA-17-92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
The vascular endothelium forms a physical barrier between blood and the surrounding tissue. Its constant exposure to haemodynamic shear stress controls endothelial barrier function which is of major importance for vascular homeostasis. The role of long non-coding RNAs (lncRNAs) in this process remains elusive. Here we identify the shear stress-induced lncRNA LASSIE (linc00520) as a stabilizer of adherens junctions (AJs) in endothelial cells (ECs), that is indispensable for normal endothelial barrier function and shear stress sensing. Silencing of LASSIE in ECs resulted in impaired cell survival, loss of cell-cell contacts and failure to align in the direction of flow. RNA affinity purification followed by mass spectrometry identified several junction proteins associated with LASSIE, including the endothelial adhesion protein PECAM-1 and intermediate filament (IF) protein nestin. Proteomic analysis of VE-cadherin-associated proteins showed that LASSIE silencing reduces VE-cadherin interaction with nestin and microtubule (MT)-associated cytoskeletal proteins. We confirmed that LASSIE silencing results in a decreased connection between VE-Cadherin and the cytoskeleton, resulting in loss of barrier function and shear stress sensing. Together, this study identifies the shear stress-induced lncRNA LASSIE as a critical link between AJs and the IF cytoskeleton, which is indispensable for normal EC junction stabilization and shear stress sensing.
Publication Title
Long non-coding RNA LASSIE regulates shear stress sensing and endothelial barrier function.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Long non-coding RNAs (lncRNAs) contribute to (patho)physiological processes in the heart. Aging is the major risk factor for cardiovascular disease and cardiomyocyte apoptosis is an underlying cause for age-related cardiac dysfunction. RNA sequencing of cardiomyocytes from young and aged mouse hearts revealed several aging-regulated lncRNAs. An siRNA screen for caspase activity identified the aging-regulated lncRNA Sarrah (ENSMUST00000140003) as anti-apoptotic, which we confirmed in human cells (human SARRAH is annotated as OXCT1-AS1). Importantly, human engineered heart tissue showed impaired contractile force development upon SARRAH knockdown compared with controls. Computational prediction of RNA-DNA triple helix formation showed that SARRAH may directly bind the promoters of genes downregulated after SARRAH silencing, which mainly consist of cell survival genes. Indeed, nuclear magnetic resonance spectroscopy confirmed RNA-DNA triple helix formation and cardiomyocytes lacking the triple helix-forming domain of Sarrah showed an increase in apoptosis. One of the key direct SARRAH targets is NRF2, an anti-oxidant transcription factor. Restoration of NRF2 levels after SARRAH silencing partially rescues the reduction in cell viability. RNA affinity purification mass spectrometry analysis identified CRIP2 as main protein interaction partner. Furthermore, SARRAH associates with acetyltransferase p300 and acetylated histone H3K27. Finally, Sarrah was also profoundly downregulated after acute myocardial infarction (AMI) in mice. Adeno-associated virus-mediated overexpression of Sarrah in mice showed better recovery of cardiac contractile function after AMI compared to control mice, as measured by echocardiography and magnetic resonance imaging, consistent with a decrease in cardiomyocyte cell death and an increase in endothelial cell proliferation. In summary, we identified the anti-apoptotic evolutionary conserved lncRNA Sarrah, which is downregulated by aging, as a pivotal regulator of cardiomyocyte survival. Sarrah overexpression has beneficial effects on AMI recovery highlighting it as a potential therapeutic approach against heart failure.
Publication Title
Aging-regulated anti-apoptotic long non-coding RNA Sarrah augments recovery from acute myocardial infarction.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
[original title] Gene expression analysis of leukemic samples derived from AF4-MLL- or AF4-MLL/MLL-AF4-transduced and transplanted hematopoietic stem/precursor cells in C57BL6 mice.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Primary human macrophages with a HIF-1alpha or HIF-2alpha knockdown were pretreated with IL-10 for 16h and afterwards for 4h additionaly under hypoxi (1% O2), RNA was isolated usind the Qiagen RNAeasy Kit and cDNA synthesis wos done using Ambion WT Expression Kit. Expression was compared to si control under control conditions.
Publication Title
Genome-wide identification of hypoxia-inducible factor-1 and -2 binding sites in hypoxic human macrophages alternatively activated by IL-10.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 21 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Susceptibility genes for Autism Spectrum Disorder (ASD), Fragile X Syndrome (FXS), monogenetic disorders with intellectual disabilities (ID) or schizophrenia (SCZ) converge on processes related to neuronal function and differentiation. Furthermore, ASD risk genes are enriched for FMRP (Fragile X Mental Retardation Protein) targets and for genes implicated in ID. In addition, a significant co-heritability was observed between ASD and SCZ. The genetic overlap between ASD, FXS, ID and SCZ together with the symptomatic differences gives rise to the question if pathomechanisms impair the same or different regulatory patterns activated during neuronal differentiation (ND). To test this idea, we performed transcriptome analysis of in-vitro differentiation of the neuroblastoma cell line model SH-SY5Y and identified genes that were differentially expressed, dynamically regulated, and coordinately expressed. The identified genetic modules activated during ND are enriched for genetic risk factors for these four disorders. Although risk genes for the disorders significantly overlap, we observed disorder specific enrichments: ASD or FXS implicated genes were likely to be positive regulators of ND whereas ID implicated genes were related to negative regulation. ASD and SCZ genes were specifically enriched among cholesterol and fatty acid associated modules. ID genes were overrepresented among cell cycle modules. In addition, we show that ASD genes are likely to be hub genes. We hypothesize that knowledge about genetic variants of an individual combined with network and pathway context of the related genes will allow differentiating between psychiatric disorders.
Publication Title
Transcriptomic signatures of neuronal differentiation and their association with risk genes for autism spectrum and related neuropsychiatric disorders.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
10 days old tumor spheroids were processed for RNA isolation using the Quiagen RNeasy Micro Kit and cDNA synthesis was done using the Ambion WT Expression Kit. Wt, HIF-1 k/d and HIF-2 k/d samples were compared to each other.
Publication Title
HIF-2alpha-dependent PAI-1 induction contributes to angiogenesis in hepatocellular carcinoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples