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GSE7345
Homo sapiens
8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The p21 RAS subfamily of small GTPases, including KRAS, HRAS, and NRAS, regulates cell proliferation, cytoskeletal organization and other signaling networks, and is the most frequent target of activating mutations in cancer. Activating germline mutations of KRAS and HRAS cause severe developmental abnormalities leading to Noonan, cardio-facial-cutaneous and Costello syndrome, but activating germline mutations of NRAS have not been reported. Autoimmune lymphoproliferative syndrome (ALPS) is the most common genetic disease of lymphocyte apoptosis and causes autoimmunity as well as excessive lymphocyte accumulation, particularly of CD4-, CD8- ab T cells. Mutations in ALPS typically affect CD95 (Fas/APO-1)-mediated apoptosis, one of the extrinsic death pathways involving tumor necrosis factor receptor (TNFR) superfamily proteins, but certain ALPS individuals have no such mutations. We show here that the salient features of ALPS as well as a predisposition to hematological malignancies can be caused by a heterozygous germline Gly13Asp activating mutation of the NRAS oncogene that does not impair CD95-mediated apoptosis. The increase in active, GTP-bound NRAS augments RAF/MEK/ERK signaling which markedly decreases the pro-apoptotic protein BIM and attenuates intrinsic, nonreceptor-mediated mitochondrial apoptosis. Thus, germline activating mutations in NRAS differ from other p21 Ras oncoproteins by causing selective immune abnormalities without general developmental defects. Our observations on the effects of NRAS activation indicate that RAS-inactivating drugs, such as farnesyl-transferase inhibitors (FTIs) should be examined in human autoimmune and lymphocyte homeostasis disorders.
Publication Title
NRAS mutation causes a human autoimmune lymphoproliferative syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background and Purpose
Publication Title
Upregulated signaling pathways in ruptured human saccular intracranial aneurysm wall: an emerging regulative role of Toll-like receptor signaling and nuclear factor-κB, hypoxia-inducible factor-1A, and ETS transcription factors.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression analysis identified a specific signature of differentially expressed genes discriminating good and poor responders in JMML patients.
Publication Title
Gene expression-based classification as an independent predictor of clinical outcome in juvenile myelomonocytic leukemia.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Adam10, a cell surface protease, cleaving many proteins including TNF-alpha and E-cadherin. Here we investigate the genome wide effects of Adam10 knock out on the transcriptome.
Publication Title
The disintegrin/metalloproteinase Adam10 is essential for epidermal integrity and Notch-mediated signaling.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Silver nanoparticles are used in consumer products like food contact materials, drinking water technologies and supplements, due to their antimicrobial properties. This leads to an oral uptake and exposure of intestinal cells. In contrast to other studies we found no apoptosis induction by surfactant coated silver nanoparticles in the intestinal cell model Caco-2 in a previous study, although the particles induced oxidative stress, morphological changes and cell death. Therefore, this study aimed to analyze the molecular mechanism of silver nanoparticles in Caco-2 cells. We used global gene expression profiling in differentiated Caco-2 cells, supported by verification of the microarray data by quantitative real time RT-PCR and microscopic analysis, impedance measurements and assays for apoptosis and oxidative stress. Our results revealed that the majority of surfactant coated silver nanoparticles are not taken up into differentiated Caco-2 cells. and probably affect the cells by outside-in signaling. They induce oxidative stress and have an influence on canonical pathways related to FAK, ILK, ERK, MAPK, integrins and adherence and tight junctions, thereby inducing transcription factors like AP1, NFB and NRF2, which mediate cellular reactions in response to oxidative stress and metal ions and induce changes in the cytoskeleton and cell-cell and cell-matrix contacts. The present data confirm the absence of apoptotic cell death. Non-apoptotic, necrotic cell death, especially in the intestine, can cause inflammation and influence the mucosal immune response.
Publication Title
Molecular mechanism of silver nanoparticles in human intestinal cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
NextSeq 500
Description
G1E cells infected with control (HMD empty vector), human GATA1, or human GATA1 mutant cDNA Overall design: 3 Biological replicates per condition for RNA-seq
Publication Title
Impaired human hematopoiesis due to a cryptic intronic <i>GATA1</i> splicing mutation.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- IlluminaHiSeq2000
Description
Rationale: VEGF family members mediate their effects through cell surface receptors VEGFR-1, VEGFR-2 and NRP. Specific ligands were used to stimulate specific combinations of the receptors to evaluate ligand and receptor properties. Objective: The properties of a novel VEGF family member Vammin were studied in level of receptor binding, gene expression in HUVECs by RNAseq and in vivo using adenoviral gene trasfers. Methods: HUVECs were trasduced using adenoviral vectors encoding VEGF-A109, VEGF-A165 and Vammin and with an empty vector as a control. Gene expression was measured using RNA sequencing. Adenoviral intramuscular gene transfers were performed into rabbit hindlimbs. Confocal and multiphoton microscopy were used for blood vessel imaging. Results and conclusions: Vammin is a highly effective VEGFR2 ligand that induces differential gene expression of genes related to proliferation, survival, angiogenesis and blood vessel development in HUVECs. The effect is stronger than ones induced by VEGF-A165 and VEGF-A109. Vammin induces highly efficient angiogenic responses when delivered into rabbit skeletal muscles using adenoviral gene transfers. Overall design: HUVEC mRNA profiles after adenoviral vector gene transfers in duplicate.
Publication Title
Snake venom VEGF Vammin induces a highly efficient angiogenic response in skeletal muscle via VEGFR-2/NRP specific signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
Rationale: Slit2 is a possible modulator of vascular endothelial growth factor (VEGF) - induced angiogenesis, but its effects have not been tested in large animal models. Objective: We studied the effect of Slit2 on therapeutic angiogenesis induced by VEGF receptor 2 (VEGFR2) ligands Vammin and VEGF-D?N?C in vivo in rabbit skeletal muscles. The Slit2 target genes were also studied by RNA sequencing (RNA-Seq) in endothelial cells. Methods and Results: Adenoviral intramuscular gene transfers were performed into rabbit hindlimbs. Confocal and multiphoton microscopy were used for blood vessel imaging. Signaling experiments and gene expression analyses were performed to study mechanisms of Slit2 action. Slit2 decreased VEGFR2-mediated vascular permeability. It also reduced VEGFR2-mediated increase in blood perfusion and capillary enlargement, whereas sprouting of the capillaries was increased. Slit2 gene transfer alone did not have any effects on vascular functions or morphology. VEGFR2 activation was not affected by Slit2, but eNOS phosphorylation was diminished. The transcriptome profiling showed Slit2 downregulating angiogenesis-related genes such as nuclear receptor subfamily 4 group A member 1 (NR4A1) and Stanniocalcin-1 (STC-1) as well as genes related to endothelial cell migration and vascular permeability. Conclusions: Combining Slit2 with VEGFs adjusts VEGFR2-mediated angiogenic effects into a more physiological direction. This possibly allows the use of higher VEGF vector doses to achieve a more widespread vector and VEGF distribution in the target tissues leading to a better therapeutic outcome while reducing excess vascular permeability. Overall design: HUVEC mRNA profiles after adenoviral vector gene transfers in duplicate.
Publication Title
Slit2 modifies VEGF-induced angiogenic responses in rabbit skeletal muscle via reduced eNOS activity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Negative-pressure wound therapy (NPWT) is widely used to improve skin wound healing and to accelerate wound bed preparation. Although NPWT has been extensively studied as a treatment for deep wounds, its effect on epithelialization of superficial dermal wounds remains unclear. To clarify the effect of NPWT on reepithelialization, we applied NPWT on split- thickness skin graft donor sites from the first postoperative day (POD) to the seventh POD. Six patients took part in the study and two samples were obtained from each. The first biopsy sample was taken at elective surgery before split-thickness skin grafting and the second one during reepithelialization on the seventh POD. In all 12 samples (eight from four NPWT patients, and four from two control patients) were collected for this study. From each sample, we carried out a comprehensive genome-wide microarray analysis. Data from patients receiving NPWT were compared groupwise with data from those not receiving NPWT.
Publication Title
Gene expression profiling of negative-pressure-treated skin graft donor site wounds.
Sample Metadata Fields
Treatment, Subject
View Samples- Bos taurus
- 23 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
This study provides the first comprehensive analysis of gene expression and transcriptome dynamics of bovine metaphase II oocytes and in vivo developing bovine embryos.
Publication Title
Genome-wide expression profiling reveals distinct clusters of transcriptional regulation during bovine preimplantation development in vivo.
Sample Metadata Fields
No sample metadata fields
View Samples