To evaluate the prognostic relevance of molecular subtypes and key transcription factors in pancreatic ductal adenocarcinoma (PDAC), we performed gene expression analysis of whole-tumor tissue obtained from 118 surgically resected PDAC and 13 control samples.
Prognostic relevance of molecular subtypes and master regulators in pancreatic ductal adenocarcinoma.
Specimen part
View SamplesTo unravel the molecular mechanisms mediating the effects of androgens on spermatogenesis, testicular gene expression was compared in mice with a Sertoli cell-selective androgen receptor knockout (SCARKO) and littermate controls on postnatal d 10. At this age testicular cell composition is still comparable in SCARKOs and controls. Microarray analysis identified 692 genes with significant differences in expression. A more than 2-fold up- or downregulation by androgen action in Sertoli cells was observed for 28 and 6 genes respectively. The biological relevance of the strongly upregulated genes was supported by the finding that several of them were previously described to be androgen-regulated or essential for spermatogenesis. Serine protease inhibitors were overrepresented in the same subgroup suggesting a role for androgens in cell junction dynamics and tissue restructuring events during spermatogenesis. A time course experiment (d8-d20), followed by cluster analysis allowed the identification of typical expression patterns of differentially expressed testicular genes during initiation of spermatogenesis. Three genes with a pattern closely resembling that of Pem, a prototypal androgen-regulated gene in Sertoli cells, were selected for confirmation by RT-PCR and further analysis. The data confirm that the SCARKO model allows identification of novel androgen-regulated genes in the testis. This particular series represents all data from d 10. The additional expression data from the time course (d8-d20) is represented by series GSE2259 ("Testicular gene expression in SCARKO mice during prepuberty").
The effect of a sertoli cell-selective knockout of the androgen receptor on testicular gene expression in prepubertal mice.
No sample metadata fields
View SamplesTo unravel the molecular mechanisms mediating the effects of androgens on spermatogenesis, testicular gene expression was compared in mice with a Sertoli cell-selective androgen receptor knockout (SCARKO) and littermate controls on postnatal d 10. At this age testicular cell composition is still comparable in SCARKOs and controls. Microarray analysis identified 692 genes with significant differences in expression. A more than 2-fold up- or downregulation by androgen action in Sertoli cells was observed for 28 and 6 genes respectively. The biological relevance of the strongly upregulated genes was supported by the finding that several of them were previously described to be androgen-regulated or essential for spermatogenesis. Serine protease inhibitors were overrepresented in the same subgroup suggesting a role for androgens in cell junction dynamics and tissue restructuring events during spermatogenesis. A time course experiment (d8-d20), followed by cluster analysis allowed the identification of typical expression patterns of differentially expressed testicular genes during initiation of spermatogenesis. Three genes with a pattern closely resembling that of Pem, a prototypal androgen-regulated gene in Sertoli cells, were selected for confirmation by RT-PCR and further analysis. The data confirm that the SCARKO model allows identification of novel androgen-regulated genes in the testis.
The effect of a sertoli cell-selective knockout of the androgen receptor on testicular gene expression in prepubertal mice.
No sample metadata fields
View SamplesThe goal of this study was to gain insight into the molecular heterogeneity of capillary endothelial cells derived from different organs by microarray profiling of freshly isolated cells and identify transcription factors that may determine the specific gene expression profile of endothelial cells from different tissues. The study focused on heart endothelial cells and presents a validated signature of 31 genes that are highly enriched in heart endothelial cells. Within this signature 5 transcription factors were identified and the optimal combination of these transcription factors was determined for specification of the heart endothelial fingerprint.
Meox2/Tcf15 heterodimers program the heart capillary endothelium for cardiac fatty acid uptake.
Sex, Specimen part
View SamplesProstate cancer is the most common male cancer and androgen receptor (AR) is the major driver of the disease. Here we show that Enoyl-CoA delta isomerase 2 (ECI2) is a novel AR-target that promotes prostate cancer cell survival. Increased ECI2 expression predicts mortality in prostate cancer patients (p=0.0086). ECI2 encodes for an enzyme involved in lipid metabolism, and we use multiple metabolite profiling platforms and RNA-seq to show that inhibition of ECI2 expression leads to decreased glucose utilization, accumulation of fatty acids and down-regulation of cell cycle related genes. In normal cells, decrease in fatty acid degradation is compensated by increased consumption of glucose, and here we demonstrate that prostate cancer cells are not able to respond to decreased fatty acid degradation. Instead, prostate cancer cells activate incomplete autophagy, which is followed by activation of the cell death response. Finally, we identified a clinically approved compound, perhexiline, which inhibits fatty acid degradation, and replicates the major findings for ECI2 knockdown. This work shows that prostate cancer cells require lipid degradation for survival and identifies a small molecule inhibitor with therapeutic potential. Overall design: Two biological replicates for prostate cancer cell line (LNCaP) and cell line representing normal prostate epithelium (RWPE-1), transfected with scrambled siRNA or two different siRNAs targeting ECI2. RNA was extracted and used for RNA-sequencing. The processed files provided are compressed folders containing multiple output files from CuffDiff runs estimating differentially expressed transcripts between the indicated ECI2 siRNA treated cells versus cells treated with Scrambled siRNAs.
Lipid degradation promotes prostate cancer cell survival.
No sample metadata fields
View SamplesSkeletal muscle senescence influences whole organism aging, yet little is known on the relay of pro-longevity signals from muscles to other tissues. We performed an RNAi screen in Drosophila for muscle-released cytokines (?myokines?) regulating lifespan and identified Myoglianin, the homolog of human Myostatin. Myoglianin is induced in skeletal muscles by the transcription factor Mnt and together they constitute an inter-organ signaling module that regulates lifespan, age-related muscle dysfunction, and protein synthesis across aging tissues. Both Mnt and Myoglianin activate already in young age the protective decline in protein synthesis that is typical of old age, while knock-down of Myoglianin impairs this process. Mechanistically, Mnt decreases the expression of nucleolar components in muscles while also decreasing nucleolar size in distant tissues via Myostatin/p38 MAPK signaling. Our results highlight a myokine-dependent inter-organ longevity pathway that coordinates nucleolar function and protein synthesis across aging tissues.
Intertissue control of the nucleolus via a myokine-dependent longevity pathway.
Sex, Specimen part, Treatment
View SamplesAnti-TNF-alpha therapy has made a significant impact on the treatment of psoriasis. Despite being designed to neutralize TNF-alpha activity, the mechanism of action of these agents in the resolution of psoriasis remains unclear. The aim of this study was to better understand the mechanism of action of etanercept by examining very early changes in the lesional skin of psoriasis patients. 20 chronic plaque psoriasis patients were enrolled and received 50mg etanercept twice weekly. Skin biopsies were obtained before treatment and on days 1, 3, 7 and 14 post-treatment. Skin mRNA expression was analysed by microarray.
Early tissue responses in psoriasis to the antitumour necrosis factor-α biologic etanercept suggest reduced interleukin-17 receptor expression and signalling.
Specimen part, Disease, Subject
View SamplesThe benefit of treatment in mild to moderate cases of E. coli mastitis in dairy cows remains a topic of discussion.
Impact of intramammary treatment on gene expression profiles in bovine Escherichia coli mastitis.
Treatment, Time
View SamplesThe Mrp8 and Mrp14 proteins (calprotectin) accumulate within tissues during aging and may contribute to chronic inflammation. To address this possibility, we evaluated calprotectin-deficient Mrp14-KO and wild-type (WT) mice at 5 and 24 months of age. However, there was no evidence that age-related inflammation is blunted in KO mice. Inflammation makers were in fact elevated in livers from old KO mice, and microarray analysis revealed more consistent elevation of genes specifically expressed by B-cells and T-cells. Adipose-specific genes, however, were less consistently elevated in aged KO mice, suggesting an anti-steatosis effect of Mrp8/14 deficiency. Consistent with this, genes decreased by the anti-steatosis agent SRT1720 were decreased in old KO compared to old WT mice. Expression of lipid metabolism genes was altered in KO mice at 5 months of age, along with genes associated with development, biosynthesis and immunity. These early-age effects of Mrp8/14 deficiency, in the absence of any external stressor, were unexpected. Taken together, our findings demonstrate a pro-steatosis rather than pro-inflammatory role of calprotectin within the aging liver. This appears to reflect a developmental-metabolic phenotype of Mrp14-KO mice that is manifest at a young age in the absence of pro-inflammatory stimuli.
Deficiency of myeloid-related proteins 8 and 14 (Mrp8/Mrp14) does not block inflammaging but prevents steatosis.
Specimen part
View SamplesBackground: Bone marrow-derived multipotent progenitor cell (MPC) transplantation leads to short term functional and bioenergetic improvement in a porcine model of postinfarction Left Ventricular (LV) remodeling despite a low engraftment rate. However, the long term outcome after MPC transplantation is unknown.
Long-term functional improvement and gene expression changes after bone marrow-derived multipotent progenitor cell transplantation in myocardial infarction.
Sex, Specimen part, Treatment
View Samples