Genome-wide association studies (GWAS) have identified genes in lipid metabolism,inflammation and vesicular trafficking pathways as risk factors for late onset Alzheimer disease (LOAD). The mechanism by which they cause AD and their relationship to the amyloid cascade affected by genes causing early onset familial AD is unknown. Unproven hypotheses are that these LOAD genes modulate the amyloid cascade itself or downstream targets affected by this cascade.If so, it is likely that these genes and/or other genes in the same pathways may show alterations in their expression as an early consequence of misprocessing of amyloid precursor protein (APP) and accumulation of amyloid -peptides (A). We report that in three independent APP transgenic mouse models of AD, multiple genes in lipid and inflammation pathways show very early changes in mRNA and protein expression. Many of these changes are reversed by treatment with LXR agonists, which regulate transcription of genes in lipid/inflammation pathways, and which we have previously shown can reverse the cognitive deficits and neuropathology in Tg2756 mice. These results suggest that changes in lipid and inflammation pathways are likely to be very early consequences of APP misprocessing and A accumulation in AD. Moreover, genetic variants within these pathways might affect risk for AD by modulating this early response. These pathways are likely to contain biomarkers of early disease and targets for therapies.
No associated publication
Age, Specimen part
View SamplesGene expression analysis in cattle embryos derived from mtDNA depleted cells in the presence and absence of Trichostatin A
No associated publication
Sex, Specimen part
View SamplesThe liver transcriptomes of two female groups (High and Low) with phenotypically extreme intramuscular fatty acid composition were sequenced using RNA-Seq [accn: SRA053452, subid: 86092, Bioproject: PRJNA168072]. A total of 146 and 180 unannotated protein-coding genes were identified in intergenic regions for the L and H groups, respectively. In addition, a range of 5.8 to 7.3% of repetitive elements was found, with SINEs being the most abundant elements. The expression in liver of 186 (L) and 270 (H) lncRNAs was also detected. The higher reproducibility of the RNA-Seq data was validated by RT-qPCR and porcine expression microarrays, therefore showing a strong correlation between RT-qPCR and RNA-Seq data (ranking from 0.79 to 0.96), as well as between microarrays and RNA-Seq (r=0.72). A differential expression analysis between H and L animals identified 55 genes differentially-expressed between groups. Pathways analysis revealed that these genes belong to biological functions, canonical pathways and three gene networks related to lipid and fatty acid metabolism. In concordance with the phenotypic classification, the pathways analysis inferred that linolenic and arachidonic acids metabolism was altered between extreme individuals. In addition, a connection was observed among the top three networks, hence suggesting that these genes are interconnected and play an important role in lipid and fatty acid metabolism.
Liver transcriptome profile in pigs with extreme phenotypes of intramuscular fatty acid composition.
Sex, Specimen part
View SamplesTranscriptome analysis of total RNA samples from HEK293-PIGS-KO and HEK293-PIGS-UBE2J1-DKO cells. To check whether KO of UBE2J1 upregulates genes of GPI biosthesis pathway, we used microarrays to analyze gene expression change by KO of UBE2J1 and comfirmed that known GPI pathway genes are not changed by ERAD-deficiency.
Cross-talks of glycosylphosphatidylinositol biosynthesis with glycosphingolipid biosynthesis and ER-associated degradation.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation.
Specimen part, Disease, Disease stage, Treatment, Subject
View SamplesThe survival of isolated metastatic cells and expansion into macroscopic tumour has been recognized as a limiting step for metastasis formation in several cancer types yet the determinants of this process remain largely uncharacterized. In colorectal cancer (CRC), we identify a transcriptional programme in tumour-associated stromal cells, which is intimately linked to a high risk of developing recurrent disease after therapy. A large proportion of CRCs display mutational inactivation of the TGF-beta pathway but paradoxically they are characterized by high TGF-beta production. In these tumours, TGF-beta instructs a transcriptional programme in stromal cells, which confers a high risk of developing metastatic disease.
Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation.
Specimen part, Disease, Disease stage, Subject
View SamplesCurrent expression profiling methods use RNA from hundreds of thousands or thousands cells. Many fields of biology can not use microarrays due to the nature of the biological systems used that are formed by hundreds or dozens of cells. Here we present a method that can handle RNA amount limitation and gives gene expression profiles from as little as 10 cells. We first validate the method hybridizing amplified RNA from MAQC samples A and B. To do that, 25 ng or 100 pg were used and expression profiles obtained as good as when compared to Affymetrix's chemistry for amplification and labeling. The same experiment was done but using sorted cells from two comercial cell lines (SW620 and SW480) obtaining the same differential expression profiling from 2000 cells or 10 cells. The central step of the method is Whole Transcriptome Amplification (WTA) from Sigma that allows the amplification of very small amounts of RNA as starting material.
Accurate expression profiling of very small cell populations.
Cell line
View SamplesThe survival of isolated metastatic cells and expansion into macroscopic tumour has been recognized as a limiting step for metastasis formation in several cancer types yet the determinants of this process remain largely uncharacterized. In colorectal cancer (CRC), we identify a transcriptional programme in tumour-associated stromal cells, which is intimately linked to a high risk of developing recurrent disease after therapy. A large proportion of CRCs display mutational inactivation of the TGF-beta pathway but paradoxically they are characterized by high TGF-beta production. In these tumours, TGF-beta instructs a transcriptional programme in stromal cells, which confers a high risk of developing metastatic disease.
Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation.
Disease, Disease stage, Subject
View SamplesUsing EphB2 or the ISC marker Lgr5, we have FACS-purified and profiled intestinal stem cells (ISCs), crypt proliferative progenitors and late transient amplifying cells to define a gene expression program specific for normal ISCs.
The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse.
Specimen part
View SamplesHmx1 is a transcription factor expressed in the developing eye and ear and in some other parts of the nervous system. Dumbo mice are carrying the Hmx1 p.Q64X loss-of-function mutation (Munroe et al., 2009. BMC Developmental Biology). Transcriptomic analyses of this mouse model allows to decipher biological pathways under the control of Hmx1. In our study, we used it to better understand the role of Hmx1 in the retina and to identify several of its target genes.
Identification of HMX1 target genes: a predictive promoter model approach.
No sample metadata fields
View Samples