Human mesenchymal stem cells circulate in 1st and early 2nd trimester fetal blood, but not in adults. Like other fetal cell types they cross the placenta, and can be found in maternal organs decades later. To determine potential ligands in human fetal mesenchymal stem cells not present in maternal blood, the gene expression of 1st trimester human fetal bone marrow, liver and blood derived mesenchymal stem cells will be compared to blood mononuclear cells from pregnant women using a Affymetrix human gene array system.
Identification of candidate surface antigens for non-invasive prenatal diagnosis by comparative global gene expression on human fetal mesenchymal stem cells.
Sex, Specimen part
View SamplesSenescence is genetically-controlled and activated in mature tissues during ageing. However, immature plant tissues also display senescence-like symptoms when continuously exposed to adverse energy-depleting conditions. We used detached dark-held immature inflorescences of Arabidopsis thaliana to understand the metabolic reprogramming occurring in immature tissues transitioning from rapid growth to precocious senescence. Macroscopic growth of the detached inflorescences rapidly ceased upon placement in water in the dark at 21C. Inflorescences were completely de-greened by 120 h of dark incubation and by 24 h had already lost 24% of their chlorophyll and 34% of their protein content. Comparative transcriptome profiling at 24 h revealed that inflorescences response at 24 h had a large carbon-deprivation component. Genes that positively regulate developmental senescence (ANAC092) and shade avoidance syndrome (PIF4 and PIF5) were up-regulated within 24 h. Mutations in these genes delayed de-greening of the inflorescences. Their up-regulation was suppressed in dark-held inflorescences by glucose treatment, which promoted macroscopic growth and development and inhibited de-greening of the inflorescences. Detached inflorescences held in the dark for 4 days were still able to re-initiat development to produce siliques upon being brought out to light indicating the transcriptional reprogramming at 24 h was adaptive and reversible. Our results suggest that the response of detached immature tissues to dark storage involves interactions between carbohydrate status sensing and light deprivation signaling and that the dark adaptive response of the tissues appears to utilize some of the same key regulators as developmental senescence.
Carbon deprivation-driven transcriptome reprogramming in detached developmentally arresting Arabidopsis inflorescences.
Specimen part, Treatment, Time
View SamplesA three-dimensional chromatin state underpins the structural and functional basis of the genome by bringing regulatory elements and genes into close spatial proximity to ensure proper, cell-type specific gene expression profiles. Here, we perform HiC chromosome conformation, ChIP-seq and RNA-seq to investigate how the three-dimensional organization of the cancer genome is disrupted in the context of epigenetic remodelling and atypical gene expression programs. Overall design: Hi-C, ChIP-seq and RNA-seq were conducted in three human prostate cell lines: normal prostate epithelial cells (PrEC) and prostate cancer cells (PC3 and LNCaP).
Three-dimensional disorganization of the cancer genome occurs coincident with long-range genetic and epigenetic alterations.
No sample metadata fields
View Samples[Hela cells]: We performed cdr2 knockdown with a pool of 4 cdr2-specific siRNAs to test whether cdr2 may regulate c-myc target genes as cells passage through mitosis.
The onconeural antigen cdr2 is a novel APC/C target that acts in mitosis to regulate c-myc target genes in mammalian tumor cells.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptomic signature of fasting in human adipose tissue.
Age, Specimen part, Subject
View SamplesLittle is known about the impact of fasting on gene regulation in human adipose tissue. Accordingly, the objective of this study was to investigate the effects of fasting on adipose tissue gene expression in humans. To that end, subcutaneous adipose tissue biopsies were collected from volunteers 2h and 26h after consumption of a standardized meal. For comparison, epididymal adipose tissue was collected from C57Bl/6J mice after a 16h fast and in the ab-libitum fed state. Transcriptome analysis was carried out using Affymetrix microarrays. We found that, 1) fasting downregulated numerous metabolic pathways in human adipose tissue, including triglyceride and fatty acid synthesis, glycolysis and glycogen synthesis, TCA cycle, oxidative phosphorylation, mitochondrial translation, and insulin signaling; 2) fasting downregulated genes involved in proteasomal degradation in human adipose tissue; 3) fasting had much less pronounced effects on the adipose tissue transcriptome in humans than mi ce; 4) although major overlap in fasting-induced gene regulation was observed between human and mouse adipose tissue, many genes were differentially regulated in the two species, including genes involved in insulin signaling (PRKAG2, PFKFB3), PPAR signaling (PPARG, ACSL1, HMGCS2, SLC22A5, ACOT1), glycogen metabolism (PCK1, PYGB), and lipid droplets (PLIN1, PNPLA2, CIDEA, CIDEC). In conclusion, although numerous genes and pathways are regulated similarly by fasting in human and mouse adipose tissue, many genes show very distinct responses to fasting in humans and mice. Our data provide a useful resource to study adipose tissue function during fasting.
Transcriptomic signature of fasting in human adipose tissue.
Specimen part
View SamplesWe''ve developed a new Method to Analyze RNA following Intracellular Sorting (MARIS) allowing us to carry out gene expression studies on cells sorted based on intracellular immunoflourescence. The purpose of this study is to determine the degree of bias that MARIS introduces on gene expression. We report RNA-seq gene expression data from human embryonic stem cells differentiated to a stage in which insulin-expressing cells are present. Gene expression data using RNA isolated from live cells is compared to gene expression data using RNA isolated from MARIS processed cells (fixed, permeabilized, antibody stained and mock sorted) to determine the degree of correlation in gene expression between these two biologically identical samples. Overall design: Human embryonic stem cells are differentiated to a stage in which insulin-expressing cells are present and split into two biologically identical samples. RNA is immediately isolated from one sample using the RNeasy protocol (live sample). RNA is isolated from the second sample following MARIS (processed sample) with all cells collected after the sort in order to keep the cell type composition between the live and processed samples the same.
MARIS: method for analyzing RNA following intracellular sorting.
No sample metadata fields
View SamplesSince fibroblasts are a key component of the stroma with an established role in cancer, we investigated the contribution of fibroblasts to the signature observed in the stromal compartment. 13 clonally derived primary stromal fibroblasts were generated from metaplasia, dysplasia and EAC specimens. Expression of a panel of known fibroblast markers and concomitant absence of epithelial markers confirmed their fibroblastic origin. Gene expression profiling of these esophageal fibroblasts demonstrated that three ontologies related to an invasive phenotype (chemotaxis, cell adhesion, regulation of angiogenesis) differentiated cancer associated from BE fibroblasts. Furthermore, the ontologies and KEGG pathways relating to inflammation were all statistically upregulated in the fibroblast signature.
Stromal genes discriminate preinvasive from invasive disease, predict outcome, and highlight inflammatory pathways in digestive cancers.
Sex, Age, Specimen part, Disease
View SamplesEicosanoids are potent regulators of gene expression of inflammatory cells. Pro- (leukotrienes B4 and C4) and anti-indflammatory (lipoxins A4 and B4) eicosanoids have been described in the literature but the detailed impact of these lipid mediators on the gene expression pattern of monocytic cells has not been studied in detail. We cultured the permanent monocytic cell line MonoMac 6 for 12 h in the absence (solvent control) and presence of these eicosanoids and quantified the differential gene expression patterns using the microarray technology.
Gene expression alterations of human peripheral blood monocytes induced by medium-term treatment with the TH2-cytokines interleukin-4 and -13.
No sample metadata fields
View SamplesDiamond-Blackfan anemia (DBA) is a rare bone marrow failure disorder that affects 7 out of 1,000,000 live births and has been associated with mutations in components of the ribosome. In order to characterize the genetic landscape of this heterogeneous disorder, we recruited a cohort of 472 individuals with a clinical diagnosis of DBA and performed whole exome sequencing (WES). We identified rare and predicted damaging mutations in likely causal genes for 78% of individuals. The majority of mutations were singletons, absent from population databases, predicted to cause loss of function, and in one of 19 previously reported ribosomal protein (RP) encoding genes. Using exon coverage estimates, we identified and validated 31 deletions in RP genes. We also observed an enrichment for extended splice site mutations and validated their diverse effects using RNA sequencing in individual-derived cell lines. Leveraging the size of our cohort, we observed robust genotype-phenotype associations with congenital abnormalities and treatment outcomes. We further identified rare mutations in 7 previously unreported RP genes that may cause DBA, as well as several distinct disorders that appear to phenocopy DBA, including 9 individuals with biallelic CECR1 mutations that result in deficiency of ADA2. However, no new genes were identified at exome-wide significance, suggesting that there are no unidentified genes containing mutations readily identified by WES that explain > 5% of DBA cases. Overall, this report should not only inform clinical practice for DBA individuals, but also the design and analysis of rare variant studies for heterogeneous Mendelian disorders. Overall design: 9 individuals with DBA with putative splice mutations and 5 control individuals were processed for RNA-seq.
The Genetic Landscape of Diamond-Blackfan Anemia.
Specimen part, Disease, Subject
View Samples