Diagnostic samples of peripheral blood form acute myeloid leukemia were analysed for gene expression differences
NFATc1 as a therapeutic target in FLT3-ITD-positive AML.
Sex, Specimen part
View SamplesIn dairy cows, administration of high dosages of niacin (NA) was found to cause anti-lipolytic effects, which are mediated by the NA receptor hydroxyl-carboxylic acid receptor 2 (HCAR2) in white adipose tissue (WAT), and thereby to an altered hepatic lipid metabolism. However, almost no attention has been paid to possible direct effects of NA in cattle liver, despite showing that HCAR2 is expressed also in the liver of cattle and is even more abundant than in WAT. Due to this, we hypothesized that feeding of rumen-protected NA to dairy cows influences critical metabolic and/or signaling pathways in the liver through inducing changes in the hepatic transcriptome. In order to identify these pathways, we applied genome-wide transcript profiling in liver biopsies obtained at 1 wk postpartum (p.p.) from dairy cows of a recent study (Zeitz et al., 2018) which were fed a total mixed ration without (control group) or with rumen-protected NA from 21 d before calving until 3 wk p.p. Hepatic transcript profiling revealed that a total of 487 transcripts were differentially expressed [filter criteria fold change (FC) > 1.2 or FC < -1.2 and P < 0.05] in the liver at 1 wk p.p. between cows fed NA and control cows. Substantially more transcripts were down-regulated (n = 338), while only 149 transcripts were up-regulated by NA in the liver of cows. Gene set enrichment analysis (GSEA) for the up-regulated transcripts revealed that the most enriched gene ontology (GO) biological process terms were exclusively related to immune processes, such as leukocyte differentiation, immune system process, leukocyte differentiation, activation of immune response and acute inflammatory response. In line with this, the plasma concentration of the acute phase protein haptoglobin tended to be increased in dairy cows fed rumen-protected NA compared to control cows (P < 0.1). GSEA of the down-regulated transcripts showed that the most enriched biological process terms were related to metabolic processes, such as cellular metabolic process, small molecule metabolic process, lipid catabolic process, organic cyclic compound metabolic process, small molecule biosynthetic process and cellular lipid catabolic process. In conclusion, hepatic transcriptome analysis shows that rumen-protected NA induces genes which are involved mainly in immune processes including acute phase response and stress response in dairy cows at wk 1 p.p. These findings indicate that supplementation of rumen-protected NA to dairy cows in the periparturient period may induce or amplify the systemic inflammation-like condition which is typically observed in the liver of high-yielding dairy cows in the p.p. period.
No associated publication
Sex, Specimen part
View SamplesAs polyphenols are exerting a broad spectrum of metabolic effects, we hypothesize that feeding of GSGME might influence other metabolic pathways in the liver which could account for the positive effects of GSGME observed in cows during early lactation. In order to investigate this hypothesis, we used using a genome-wide transcript profiling technique to explore changes in the hepatic transcriptome of cows supplemented with GSGME during the transition period. Transcriptomic analysis of the liver revealed 207 differentially expressed transcripts (fold change > 1.3 or < -1.3, P < 0.05), from which 156 (155 mRNAs, 1 miRNA) were up- and 51 (43 mRNAs, 8 miRNAs) were down-regulated, between cows fed GSGME and control cows. Gene set enrichment analysis of the 155 up-regulated mRNAs showed that the most enriched gene ontology (GO) biological process terms were dealing with cell cycle regulation, such as M phase, cell cycle phase, mitotic cell phase and microtubule cytoskeleton and the most enriched KEGG database pathways were p53 signaling and cell cycle. Functional analysis of the 43 down-regulated mRNAs revealed that 13 genes (XBP1, HSPA5, HERPUD1, DNAJC5G, CALR, PDIA4, DNAJB11, PHLDA1, PPP1R3C, GADD45B, BAG3, HYOU1, MANF) are involved in ER stress-induced UPR. Moreover, several of the down-regulated mRNAs, like CXCL14 and CCL3L1L and the acute phase protein SAA4, play an important role in inflammatory processes. Accordingly, protein folding, response to unfolded protein, response to protein stimulus, unfolded protein binding, chemokine activity, chemokine receptor binding and heat shock protein binding were identified as one of the most enriched GO biological process and molecular function terms assigned to the down-regulated genes. In line with the transcriptomics data the plasma concentrations of the acute phase proteins SAA and haptoglobin were reduced in cows fed GSGME compared to control cows. Collectively, our findings from transcriptome analysis of down-regulated mRNAs and functional analysis of mRNAs targeted by the up-regulated mir-376c clearly indicate that GSGME is able to inhibit inflammatory processes and ER stress in the liver of dairy cows during early lactation. Moreover, our findings indicate that at least some of the GSGME effects on the hepatic transcriptome of dairy cows are mediated by miRNA-mRNA interactions.
Analysis of hepatic transcript profile and plasma lipid profile in early lactating dairy cows fed grape seed and grape marc meal extract.
Sex, Specimen part
View SamplesIn the present study, transcript profiling was carried out in the liver samples from wk 5 of lactation in order to identify genes and pathways regulated by rumen-protected CLA during early lactation. The first wks after parturition represent a critical phase in the productive cycle of high-yielding dairy cows because the liver experiences pronounced metabolic and inflammatory stress which increases the risk to develop liver-associated diseases, such as fatty liver and ketosis.
Transcript profiling in the liver of early-lactating dairy cows fed conjugated linoleic acid.
Sex, Specimen part
View SamplesWe determined and classified Yak1-regulated genes in haploid strains of the Sigma1278b genetic background under vegetative growth conditions. For this purpose, we measured transcriptional profiles of different haploid MATa yeast strains of the following genotypes:YAK1 (468=YHUM0468), yak1 (1313=YHUM1313), strain YHUM1313 (yak1) carrying a high copy plasmid with YAK1 (1313Yhc) and strain YHUM1313 (yak1) carrying a high copy plasmid with YAK1 K398R (1313KDhc). All strains were grown in duplicate in YNB medium supplemented with tryptophan at 30 degrees Celsius to an optical density of 1.0 before extraction of total RNA and transcriptional profiling.
No associated publication
Sex
View SamplesBackground: While the mechanisms underlying the lactation-induced adaptations of intermediary metabolism and immune response have been extensively studied in rodents and dairy cows, little is known in this regard in sows. Therefore, the present study aimed to explore the lactation-induced changes in hepatic gene expression in sows during lactation.
Genome-wide transcript profiling indicates induction of energy-generating pathways and an adaptive immune response in the liver of sows during lactation.
Sex, Specimen part
View SamplesWe determined and classified Whi3-regulated genes in haploid strains of the Sigma1278b genetic background under vegetative growth conditions. For this purpose, we measured transcriptional profiles of two different haploid MATa yeast strains of the following genotypes: WHI3 strain (468=YHUM0468) and whi3 strain (1105=YHUM1105).Both starins were grown in duplicate in YNB medium with tryptophan at 30°C to an optical density of 1.0 before extraction of total RNA and transcriptional profiling
No associated publication
Sex
View SamplesWe identified Ncoa3 as a regulator of neuronal morphology and microRNA activity. In order to uncover target genes of this transcriptional coactivator we performed this microarray analysis.
A large-scale functional screen identifies Nova1 and Ncoa3 as regulators of neuronal miRNA function.
Specimen part, Treatment
View SamplesNon-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Liver samples from morbidly obese patients (N=45) with all stages of NAFLD and controls (N=18) were analysed by array-based DNA methylation and mRNA expression profiling. NAFLD-specific expression and methylation differences were seen for nine genes coding for key enzymes in intermediate metabolism (including PC, ACLY, PLCG1) and insulin/insulin-like signalling (including IGF1, IGFBP2, PRKCE) and replicated by bisulfite pyrosequening (independent N=39). Transcription factor binding sites at NAFLD-specific CpG sites were >1000-fold enriched for ZNF274, PGC1A and SREBP2. Intra-individual comparison of liver biopsies before and after bariatric surgery showed NAFLD-associated methylation changes to be partially reversible. Post-bariatric and NAFLD-specific methylation signatures were clearly distinct both in gene-ontology and transcription factor binding site analyses, with >400-fold enrichment of NRF1, HSF1 and ESRRA sites. Our findings provide one of the first examples of treatment-induced epigenetic organ remodelling in humans.
DNA methylation analysis in nonalcoholic fatty liver disease suggests distinct disease-specific and remodeling signatures after bariatric surgery.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Nijmegen Breakage Syndrome fibroblasts and iPSCs: cellular models for uncovering disease-associated signaling pathways and establishing a screening platform for anti-oxidants.
Specimen part, Disease, Disease stage, Cell line
View Samples