Filters
Technology
Platform
SRP057996
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
- 183 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
183 breast tumors from the Helsinki Univerisity Central Hospital with survival information
Publication Title
Variants on the promoter region of PTEN affect breast cancer progression and patient survival.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
A mouse AGM-derived cell line, AGM-s3, was shown to support the development of hematopoietic stem cells. To elucidate the molecular mechanisms regulating early hematopoiesis, we obtained subclones from AGM-s3, some of which were hematopoiesis supportive (s3-A9) and others which were non-supportive (s3-A7), and we analyzed the gene expression profiles by gene chip analysis.
Publication Title
Expression profile analysis of aorta-gonad-mesonephros region-derived stromal cells reveals genes that regulate hematopoiesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The nuclear hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates its target genes via activation of the transcription factor vitamin D receptor (VDR) far more specifically than the chromatin modifier trichostatin A (TsA) via its inhibitory action on histone deacetylases. We selected the thrombomodulin gene locus with its complex pattern of three 1,25(OH)2D3 target genes, five VDR binding sites and multiple histone acetylation and open chromatin regions as an example to investigate together with a number of reference genes, the primary transcriptional responses to 1,25(OH)2D3 and TsA. Transcriptome-wide, 18.4% of all expressed genes are either up- or down-regulated already after a 90 min TsA treatment; their response pattern to 1,25(OH)2D3 and TsA sorts them into at least six classes. TsA stimulates a far higher number of genes than 1,25(OH)2D3 and dominates the outcome of combined treatments. However, 200 TsA target genes can be modulated by 1,25(OH)2D3 and more than 1000 genes respond only when treated with both compounds. The genomic view on the genes suggests that the degree of acetylation at transcription start sites and VDR binding regions may determine the effect of TsA on mRNA expression and its interference with 1,25(OH)2D3. Our findings may have implications on dual therapies using chromatin modifiers and nuclear receptor ligands.
Publication Title
Chromatin acetylation at transcription start sites and vitamin D receptor binding regions relates to effects of 1α,25-dihydroxyvitamin D3 and histone deacetylase inhibitors on gene expression.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip, Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
SUMOylation modulates the transcriptional activity of androgen receptor in a target gene and pathway selective manner.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
Androgen receptor (AR) plays an important regulatory role during prostate cancer development. ARs transcriptional activity is regulated by androgenic ligands, but also by post-translational modifications. To study the role of the AR SUMOylation in genuine chromatin environment, we compared androgen-regulated gene expression and AR chromatin occupancy in PC-3 prostate cancer and HEK293 cell lines stably expressing wild-type (wt) or SUMOylation site-mutated AR (AR-K386R,K520R). Our genome-wide gene expression analyses reveal that the SUMOylation modulates the AR function in a target gene and pathway selective manner. The transcripts that are differentially regulated by androgen and SUMOylation are linked to cellular movement, cell death, cellular proliferation, cellular development and cell cycle. In line with these data, SUMOylation mutant AR cells proliferate faster and are more sensitive to apoptosis. Moreover, ChIP-seq analyses show that the SUMOylation modulates the chromatin occupancy of AR on many loci in a fashion that parallels with their differential androgen-regulated expression. De novo motif analyses show that other transcription factor-binding motifs are differentially enriched at the wtAR- and the AR-K386R,K520R-preferred genomic binding positions. Taken together, our data indicate that SUMOylation does not simply repress the AR activity, but it regulates ARs interaction with the chromatin and the receptors target gene selection.
Publication Title
SUMOylation modulates the transcriptional activity of androgen receptor in a target gene and pathway selective manner.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Necroptosis microenvironment directs lineage commitment in liver cancer.
Sample Metadata Fields
Sex, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Primary liver cancer represents a major health problem. It comprises hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), which differ markedly with regards to their morphology, metastatic potential and therapy response. Yet, molecular actors and tissue context that commit transformed hepatic cells towards HCC or ICC are largely unknown. Here, we report that the hepatic microenvironment epigenetically shapes lineage commitment in mosaic mouse models of liver tumourigenesis. While a necroptosis associated hepatic cytokine microenvironment determines ICC outgrowth from oncogenically transformed hepatocytes, hepatocytes harbouring identical oncogenic drivers give rise to HCC if surrounded by apoptotic hepatocytes. Epigenome and transcriptome profiling of murine HCC and ICC singled out Tbx3 and Prdm5 as major microenvironment-dependent and epigenetically regulated lineage commitment factors, a function conserved in humans. Together, our study provides unprecedented insights into lineage commitment in liver tumourigenesis and explains molecularly why common liver damaging risk factors can either lead to HCC or ICC.
Publication Title
Necroptosis microenvironment directs lineage commitment in liver cancer.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Primary liver cancer represents a major health problem. It comprises hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), which differ markedly with regards to their morphology, metastatic potential and therapy response. Yet, molecular actors and tissue context that commit transformed hepatic cells towards HCC or ICC are largely unknown. Here, we report that the hepatic microenvironment epigenetically shapes lineage commitment in mosaic mouse models of liver tumourigenesis. While a necroptosis associated hepatic cytokine microenvironment determines ICC outgrowth from oncogenically transformed hepatocytes, hepatocytes harbouring identical oncogenic drivers give rise to HCC if surrounded by apoptotic hepatocytes. Epigenome and transcriptome profiling of murine HCC and ICC singled out Tbx3 and Prdm5 as major microenvironment-dependent and epigenetically regulated lineage commitment factors, a function conserved in humans. Together, our study provides unprecedented insights into lineage commitment in liver tumourigenesis and explains molecularly why common liver damaging risk factors can either lead to HCC or ICC.
Publication Title
Necroptosis microenvironment directs lineage commitment in liver cancer.
Sample Metadata Fields
Sex, Cell line
View Samples