Administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extends the lifespan of various model organisms including yeast, flies and worms. In ageing yeast, spermidine treatment triggeres epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), leading to induction of autophagy and thereby suppressing oxidative stress and necrosis. In order to further characterize the effects by spermidine supplementation of aging yeast cultures and to understand how global histone deacetylation affects gene transcription during aging, Affymetrix-based microarray analyses of three day old as well as ten day old cultures with and without administration of spermidine was performed.
Induction of autophagy by spermidine promotes longevity.
Age, Compound, Time
View SamplesRNA-seq involves purification of RNA, followed by either selection of poly-A(+) RNA or depletion of ribosomal RNA. RNA is then converted into cDNA by one of two methods; 1) random priming, followed by cDNA fragmentation, end-repair and Illumina/SOLiD linker ligation or, 2) Enzymatic or chemical RNA fragmentation followed by linker ligation and cDNA generation. Following PCR amplification of tailed cDNA fragments with primers suitable for solid phase (Illumina) or emPCR (SOLiD) clonal amplification RNA-seq libraries are subjected to sequencing. Sequence alignment software is then used to compare the short sequence reads to reference genome and transcriptome databases, and exon-exon junction databases. From this analysis paradigm emerges data that is used for a variety of purposes, including the measurement of gene- level and exon-level expression abundance; detection of base changes (mutations and polymorphisms) relative to reference datasets; measurement of alternative splicing events; identification of gene fusion events; and identification of RNA editing events.
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Sex, Age, Specimen part, Disease, Race
View SamplesTo gain insights into the molecular mechanisms underlying the memory consolidation in Drosophila melanogaster, isolated mushroom bodies were subjected to RNA-seq analysis at several time points after a conditioning that induces CREB-dependent olfactory aversive memory.
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No sample metadata fields
View SamplesWe performed genome-wide methylation analysis of primary feto-placental arterial and venous endothelial cells from healthy (AEC and VEC) and GDM complicated pregnancies (dAEC and dVEC). Parallel transcriptome analysis identified variation in gene expression linked to GDM-associated DNA methylation, implying a direct functional link. Pathway analysis found that genes altered by exposure to GDM clustered to functions associated with Cell Morphology and Cellular Movement in both AEC and VEC. Further functional analysis demonstrated that GDM exposed cells have altered actin organization and barrier function.
Human fetoplacental arterial and venous endothelial cells are differentially programmed by gestational diabetes mellitus, resulting in cell-specific barrier function changes.
Specimen part
View SamplesAs susceptibility to many adult disorders originates in utero, we here hypothesized that fetal sex influences gene expression in placental cells and produces functional differences in human placentas. We found that fetal sex differentially affects gene expression in a cell-phenotype dependent manner among all four placental cell-phenotypes studied: cytotrophoblasts, syncytiotrophoblasts, arterial endothelial cells and venous endothelial cells. The markedly enriched pathways in males were identified to be signaling pathways for graft-versus-host disease as well as the immune and inflammatory systems, both supporting the hypothesis that there is reduced maternal-fetal compatibility for male fetuses.
The human placental sexome differs between trophoblast epithelium and villous vessel endothelium.
Sex, Specimen part
View SamplesHypoxia triggers aggressive cancer growth and contributes to chemotherapy resistance. Novel therapeutic strategies aim at targeting hypoxia activated signaling pathways. Tumor hypoxia not only affects neoplastic tumor cells but also the surrounding stroma cells. Therefore, a novel ex vivo model was established, which allows the study of hypoxia effects in fragments of non-small cell lung cancer (NSCLC) with preserved tumor microenvironment and 3D-structure. Microarray analysis identified 107 significantly regulated genes with at least two-fold expression change in hypoxic compared to normoxic fragments. However, only four genes were significantly regulated in both subtypes, adenocarcinoma and squamous cell carcinoma. The hypoxic regulation of these four genes was verified in an independent set using quantitative PCR.
Hypoxia increases membrane metallo-endopeptidase expression in a novel lung cancer ex vivo model - role of tumor stroma cells.
Specimen part, Treatment
View SamplesHuman testicular cells were isolated mechanically and enzymatically from testis of braindead donors and from urological samples. The expression of genes was studied at baseline and 1,25(OH)2D treated conditions.
Testicular synthesis and vitamin D action.
Specimen part
View SamplesWe assessed the response of primary cultures of human trophoblasts to bioactive 1,25 (OH)2D3 and used whole genome microarray to identify innovative hypotheses.
No associated publication
Specimen part, Treatment
View SamplesBackground: Non-coding RNAs and especially microRNAs have been discovered as master regulators of cancer initiation and progression. The aim of our study was to discover and characterize the function of yet uncharacterized microRNAs in human breast carcinogenesis. Methods: In an unbiased approach, we made use of a commonly used model system for breast cancer (BC) stem cells (mammospheres) to identify whole miRNome alterations with a special focus on previously uncharacterized miRNAs in BC. We further characterized the influence of microRNA-1287-5p, a yet uncharacterized microRNA in BC, in patient samples (n=1262) and on several hallmarks of cancer in vitro and in vivo with a special focus on triple negative BC. The molecular mode of action was further characterized using whole transcriptome analysis, in silico prediction tools, miRNA-interaction luciferase assays and pheno-copy assays. Results: We identified miR-1287-5p among many others as differentially expressed in mammospheres. Clinical validation indicated that miR-1287-5p is significantly downregulated in human BC and associated with poor prognosis. This clinical finding can be explained by miR-1287-5p mediated growth inhibitory effects, G1 cell cycle arrest, decreased anchorage-independent growth and tumor growth in vivo. Finally, we identified PIK3CB as a direct molecular interactor of miR-1287-5p and a pheno-copy factor for miR-1287-5p. Finally, targeting PI3K-signaling pathway with chemical inhibitors together with miR-1287-5p mimics increased the pharmacological growth inhibitory potential. Conclusion: In conclusion, our data identified for the first time an involvement of miR-1287-5p in human BC and suggest a potential for therapeutic interventions in hardly to treat triple negative BC.
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Cell line
View SamplesMicroarray profiling was used to determine the most abundantly expressed genes in spinophilin-silenced breast cancer cells compared to control cells in the cell line SUM159. We identified several differentially expressed genes in spinophilin-silenced cells.
No associated publication
Cell line
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