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GSE27831
Homo sapiens
27 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Uveal melanoma is an aggressive cancer that metastasizes to the liver in about half of patients, being at that time almost always fatal. Identification of patients at high risk of metastases may provide indication for a frequent follow-up for early detection of metastases and treatment. The analysis of the gene expression profiling of primary human uveal melanomas showed high expression of SDCBP (encoding for syndecan-binding protein-1 or syntenin-1), which appeared higher in patients with recurrence, whereas expression of syndecans was lower and unrelated to progression. Moreover, we found that high expression of SDCBP gene was related to metastatic progression in two additional independent dataset of uveal melanoma patients. More importantly, immunohistochemistry showed that high expression of syntenin-1 protein in primary tumours was significantly related to metastatic recurrence in our cohort of patients. Syntenin-1 expression was confirmed by RT-PCR, immunofluorescence and immunohistochemistry in cultured uveal melanoma cells or primary tumours. A pseudo-metastatic model of uveal melanoma to the liver was developed in NOD/SCID/IL2R null mice and the study of syntenin-1 expression in primary and metastatic lesions revealed higher syntenin-1 expression in metastases. The inhibition of SDCBP expression by siRNA impaired the ability of uveal melanoma cells to migrate in a woundhealing assay. These results suggest that SDCBP is involved in uveal melanoma progression and that it represents a candidate molecular marker of metastases and a potential therapeutic target.
Publication Title
Mda-9/syntenin is expressed in uveal melanoma and correlates with metastatic progression.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
Illumina HiSeq 2500
Description
Pluripotent cell identity comprises a spectrum of cell states including naive and primed states, which are typified by mouse embryonic stem cells (ESCs) and epiblast-derived stem cells (EpiSCs), respectively. Here we define a pluripotent cell fate (PCF) gene signature based on RNA-seq analysis associated with naive and primed pluripotency acquisition, and identify Zfp281 as a key transcriptional regulator for primed pluripotency and also as a barrier to achieve the naive pluripotency of both mouse and human ESCs. Overall design: RNA sequencing analysis was performed in WT and Zfp281 null mouse embryonic stem cells under different pluripotent culture conditions. RNA-seq Experiments were carry out in two biological replciates. Genome binding/occupancy profiling of Zfp281 was performed in mouse embryonic stem cells by ChIP sequencing.
Publication Title
Zfp281 Coordinates Opposing Functions of Tet1 and Tet2 in Pluripotent States.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The SIN3A/HDAC Corepressor Complex Functionally Cooperates with NANOG to Promote Pluripotency.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Multiple myeloma (MM)-induced osteoclast (OC) formation occurs in close contact with MM cell infiltration into the bone marrow (BM) due to the imbalance of the receptor activator of NF-kappa-B ligand (RANKL)/osteoprotegerin (OPG) ratio in favor of RANKL in the micorenvironment. Soluble factors including CCL3/MIP-1?, IL7 and IL-3 also contribute to the increased OC formation in MM.The immunomodulatory drugs (IMiDs) directly inhibit OCs, however their effect on the mechanisms involved in MM-induced OC formation are not known and have been investigated in this study. We found that both Lenalidomide (LEN) and Pomalidomide (POM), at concentration ranging reached in vivo, significantly blunted RANKL up-regulation normalizing the RANKL/OPG ratio in human BM osteoprogenitor cells (PreOBs) co-cultured with MM cells and inhibited CCL3/MIP-1? production by MM cells. The reduction of CD49d expression on MM cells, a molecule critically involved in RANKL up-regulation in the micorenvironment, accompanied this effect. Consistently the pro-osteoclastogenic property of the conditioned medium of MM cells co-cultured with PreOBs was reduced in the presence of both IMiDs. By microarray analysis we further investigated the effect of POM and LEN on the transcriptional profile of both MM cells and PreOBs. We found a significant down-regulation in MM cells, in addition to CD49d, of genes belonging to the adhesion molecules family such as ITGA8 and ICAM2 (CD102) induced by both IMiDs compounds. In conclusion our data suggest that POM and LEN inhibits MM-induced OC formation through the inhibition of RANKL/OPG ratio targeting the expression of adhesion molecules by MM cells.
Publication Title
Immunomodulatory drugs lenalidomide and pomalidomide inhibit multiple myeloma-induced osteoclast formation and the RANKL/OPG ratio in the myeloma microenvironment targeting the expression of adhesion molecules.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Despite the requirement of Sin3a for survival of early embryos and embryonic stem cells (ESCs), mechanistic action of Sin3a in the maintenance and establishment of pluripotency remains unexplored. Here we report the transcriptional regulatory roles of Sin3a in maintaining ESC pluripotency and in reprogramming somatic cells towards full pluripotency. Sin3a/HDAC complex members were enriched in an extended Nanog interactome and exhibited a predominant transcriptional co-activator role at a global level in ESCs. We also established a critical role for Sin3a in efficient reprogramming of somatic cells towards full pluripotency. Nanog and Sin3a co-localize at almost all of their genome-wide targets in pre-iPSCs, and both factors are required to directly induce a synergistic transcriptional program wherein pluripotency genes are activated and reprogramming barrier genes are repressed. Our results, for the first time, establish positive roles of the Sin3a/HDAC complex in the maintenance and establishment of pluripotency.
Publication Title
The SIN3A/HDAC Corepressor Complex Functionally Cooperates with NANOG to Promote Pluripotency.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Myeloma bone disease is characterized by tremendous bone destruction with suppressed bone formation. IL-3 is a multifunctional cytokine that increases myeloma cell growth and osteoclast proliferation while inhibiting osteoblast differentiation. While IL-3 appears to be an attractive therapeutic target for myeloma, attempts at targeting IL-3 have been unsuccessful due to IL-3s effects on normal hematopoiesis. Thus identification of IL-3s downstream effects in MMBD is important for effective targeting of this cytokine in MM. Here we demonstrated that treatment of myeloma patient CD14+ bone marrow monocyte / macrophages with IL-3 induces high levels of Activin A (ActA), a pluripotent TGF- superfamily member that, like IL-3, modulates MMBD by enhancing osteoclastogenesis and inhibiting osteoblasts. We show that IL-3 induced osteoclastogenesis is mediated by ActA and is RANKL independent. Additionally, IL-3 induced ActA secretion is greatest early in osteoclastogenesis and ActA acts early in osteoclastogenesis. Therefore we suggest that therapies targeting ActA production should block IL-3s effects in myeloma bone disease.
Publication Title
Bone marrow monocyte-/macrophage-derived activin A mediates the osteoclastogenic effect of IL-3 in multiple myeloma.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Gallus gallus
- 56 Downloadable Samples
- Illumina HiSeq 2000
Description
Background: Avian infectious bronchitis (IB) is an acute and highly contagious disease of the upper-respiratory tract caused by infectious bronchitis virus (IBV). Understanding the molecular mechanisms involved in the interaction between innate and adaptive immune responses to IBV infection is a crucial element for further improvements in strategies to control IB. To this end, two chicken lines, selected for high and low serum concentration of mannose-binding lectin (MBL), a soluble pattern recognition receptor, were studied. In total, 32 birds from each line (designated L10H for high and L10L for low MBL serum concentration, respectively) were used. Sixteen birds from each line were infected with IBV at 3 weeks of age and sixteen birds were left uninfected. Eight uninfected and eight infected birds from each line were euthanized at 1 and 3 weeks post infection. RNA sequencing was performed on spleen samples from all 64 birds used in the experiment. Differential gene expression analysis was performed for four comparisons: L10L line versus L10H line for uninfected birds at weeks 1 and 3, respectively, and L10L line versus L10H line for infected birds at weeks 1 and 3, respectively. Functional analysis based on the differentially expressed genes was performed using Gene Ontology (GO) Immune System Process terms specific for Gallus gallus. Results: Comparing uninfected L10H and L10L birds, we identified 1698 and 1424 differentially expressed (DE) genes at weeks 1 and 3, respectively. For the IBV-infected birds, 1934 and 866 DE genes were identified between the two lines at weeks 1 and 3, respectively. In both cases DE genes had FDR-adjusted p-value <0.05. The two most enriched GO terms emerging from the comparison of uninfected birds between the two lines were “Lymphocyte activation involved in immune response” (GO:0002285) and “Somatic recombination of immunoglobulin genes involved in immune response” (GO:0002204) at weeks 1 and 3, respectively. When comparing IBV-infected birds between the two lines, the most enriched GO terms were “Alpha-beta T cell activation” (GO:0046631) and “Positive regulation of leukocyte activation” (GO:0002696) at weeks 1 and 3, respectively. Conclusion: Healthy birds from the two lines showed significant differences in expression profiles for subsets of both adaptive and innate immunity-related genes, whereas comparison of the IBV-infected birds from the two lines showed differences in expression of immunity-related genes involved in T cell activation and proliferation. The observed transcriptome differences between the two lines indicate that selection for MBL had a much wider effect than solely on serum MBL concentration, and in addition influenced the innate and adaptive immune responses. Future research will focus on identifying signatures of selection in order to further understand molecular pathways be responsible for differences between the two lines as well as for efficient IBV immune protection. Overall design: For this study 64 spleen samples were harvested and used for RNA sequencing from birds originating from the two Aarhus University inbred lines, L10H and L10L. The birds were infected at age of 3 weeks and they were sacrificed 1 and 3 weeks post infection by cervical dislocation and spleen samples were collected. At both time points, eight samples from the two lines, L10H and line L10L, from each group (uninfected and infected) were collected.
Publication Title
RNA sequencing-based analysis of the spleen transcriptome following infectious bronchitis virus infection of chickens selected for different mannose-binding lectin serum concentrations.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Genes are up and down regualted in DRG and spinal dorsal cord after peripheral nerve injury Overall design: WT male adult with sciatic and femoral nerve transection 7 days, RNA was purified from ipilateral or contralateral L4-L6 DRGs or lumbar spinal dorsal cords
Publication Title
Injured sensory neuron-derived CSF1 induces microglial proliferation and DAP12-dependent pain.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Adipose tissue plays an important role in storing excess nutrients and preventing ectopic lipid accumulation in other organs. Obesity leads to excess lipid storage in adipocytes, resulting in the generation of stress signals and the derangement of metabolic functions. SIRT1 is an important regulatory sensor of nutrient availability in many metabolic tissues. Here we report that SIRT1 functions in adipose tissue to protect from the development of inflammation and obesity under normal feeding conditions, and the progression to metabolic dysfunction under dietary stress. Genetic ablation of SIRT1 from adipose tissue leads to gene expression changes that highly overlap with changes induced by high fat diet in wild type mice, suggesting that dietary stress signals inhibit the activity of SIRT1. Indeed, we show that high fat diet induces the cleavage of SIRT1 in adipose tissue by the inflammation-activated caspase-1, providing a link between dietary stress and predisposition to metabolic dysfunction.
Publication Title
High-fat diet triggers inflammation-induced cleavage of SIRT1 in adipose tissue to promote metabolic dysfunction.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In multiple myeloma (MM), hypoxia-inducible transcription factor-1 (HIF-1) is overexpressed in the MM cells of the hypoxic bone marrow (BM) microenvironment. Herein, we explored in MM cells the in vitro and in vivo effects of persistent HIF-1 inhibition by expression of a lentivirus shRNA pool on proliferation, survival and transcriptional and pro-angiogenic profiles. Among the significantly modulated genes (326 and 361 genes in hypoxic and normoxic condition, respectively), we found that HIF-1 inhibition in the human myeloma cell line JJN3 downregulates the pro-angiogenic molecules VEGF, IL8, IL10, CCL2, CCL5, and MMP9. Interestingly, several pro-osteoclastogenic cytokines were also inhibited, such as IL-7 and CCL3/MIP-1. The effect of HIF-1 inhibition was assessed in vivo in NOD/SCID mice both in subcutaneous and intratibial models, indicating in either case a dramatic reduction of weight and volume of the tumor burden as a consequence of HIF-1 knockdown. Moreover, a significant reduction of the number of vessels per field and VEGF immunostaining were observed. Finally, in the intra-tibial experiments, HIF-1 inhibition significantly blocks JJN3-induced bone destruction. Overall, our data indicate that HIF-1 suppression in MM cells significantly blocks MM-induced angiogenesis and reduces both tumor burden and bone destruction in vivo, strongly indicating HIF-1 as an emerging therapeutic target in MM.
Publication Title
Hypoxia-inducible factor (HIF)-1α suppression in myeloma cells blocks tumoral growth in vivo inhibiting angiogenesis and bone destruction.
Sample Metadata Fields
Specimen part, Cell line
View Samples