PMK-1 is involved in the heat stress response of C. elegans, translocates to the nucleus upon heat exposure and influences the expression of chaperone genes, proteasomal subunits and protein-biosynthesis related genes. Overall design: Differential Gene expression of WT and pmk-1 deletion mutant (KU25) after 5 hours at 35°C
The p38 MAPK PMK-1 shows heat-induced nuclear translocation, supports chaperone expression, and affects the heat tolerance of Caenorhabditis elegans.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cardiac transcriptome profiling of diabetic Akita mice using microarray and next generation sequencing.
Specimen part
View SamplesHow organ size and form are controlled during development is a major question of biology. Blood vessels have been shown to be essential for early development of the liver and pancreas, and are fundamental to normal and pathological tissue growth. Here we report that non-nutritional signals from blood vessels surprisingly act to restrain pancreas growth. Elimination of endothelial cells increases the size of embryonic pancreatic buds. Conversely, VEGF-induced hypervascularization decreases pancreas size. The growth phenotype results from vascular restriction of pancreatic tip cell formation, lateral branching and differentiation of the pancreatic epithelium into endocrine and acinar cells. The effects are seen both in vivo and ex vivo, indicating a perfusion-independent mechanism. Thus the vasculature controls pancreas morphogenesis and growth by reducing branching and differentiation of primitive epithelial cells.
Blood vessels restrain pancreas branching, differentiation and growth.
Specimen part
View SamplesAdenosine to Inosine (A-to-I) RNA editing is a site-specific modification of RNA transcripts, catalyzed by members of the ADAR (Adenosine Deaminase Acting on RNA) protein family. RNA editing occurs in human RNA in thousands of different sites. Some of the sites are located in protein-coding regions but the majority is found in non-coding regions, such as 3UTRs, 5UTRs and introns - mainly in Alu elements. While editing is found in all tissues, the highest levels of editing are found in the brain. It was shown that editing levels within protein-coding regions are increased during embryogenesis and after birth and that RNA editing is crucial for organism viability as well as for normal development. In this study we characterized the A-to-I RNA editing phenomenon during neuronal and spontaneous differentiation of human embryonic stem cells (hESCs). We identified high editing levels of Alu repetitive elements in hESCs and demonstrated a global decrease in editing levels of non-coding Alu sites when hESCs are differentiating, particularly into the neural lineage. Using RNA interference, we showed that the elevated editing levels of Alu elements in undifferentiated hESCs are highly dependent on ADAR1. DNA microarray analysis showed that ADAR1 knockdown has a global effect on gene expression in hESCs and leads to a significant increase in RNA expression levels of genes involved in differentiation and development processes, including neurogenesis. Taken together, our data suggest that A-to-I editing of Alu sequences plays a role in the regulation of hESC early differentiation decisions.
Alu sequences in undifferentiated human embryonic stem cells display high levels of A-to-I RNA editing.
Specimen part
View SamplesIn multigravidae, a specific dNK cell population characterized by NKG2CBright expression is expanded, suggesting that this reflects a population of memory dNK generated during the first pregnancy. Purpose: To gain further insight into the transcriptome profile of the expanded memory NKG2CBright dNK population found only in multigravida decidua samples Overall design: Flow cytometry based dNK cell sorting (based on CD56 and NKG2C) was done in order to purify CD56PosCD3NegCD16NegNKG2CBright and CD56PosCD3NegCD16NegNKG2CNeg subsets.
Trained Memory of Human Uterine NK Cells Enhances Their Function in Subsequent Pregnancies.
Specimen part, Subject
View SamplesObjective: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here we aim to investigate the interaction between adipose tissue and liver in NAFLD, and identify potential early plasma markers that predict NASH. Research Design and Methods: C57Bl/6 mice were chronically fed a high fat diet to induce NAFLD and compared with mice fed low fat diet. Extensive histological and phenotypical analyses coupled with a time-course study of plasma proteins using multiplex assay was performed. Results: Mice exhibited pronounced heterogeneity in liver histological scoring, leading to classification into 4 subgroups: LF-low (LFL) responders displaying normal liver morphology, LF-high (LFH) responders showing benign hepatic steatosis, HF-low (HFL) responders displaying pre-NASH with macrovesicular lipid droplets, and HF-high (HFH) responders exhibiting overt NASH characterized by ballooning of hepatocytes, presence of Mallory bodies, and activated inflammatory cells. Compared to HFL responders, HFH mice gained weight more rapidly and exhibited adipose tissue dysfunction characterized by decreased final fat mass, enhanced macrophage infiltration and inflammation, and adipose tissue remodelling. Plasma haptoglobin, IL-1, TIMP-1, adiponectin and leptin were significantly changed in HFH mice. Multivariate analysis indicated that in addition to leptin, plasma CRP, haptoglobin, eotaxin and MIP-1 early in the intervention were positively associated with liver triglycerides. Intermediate prognostic markers of liver triglycerides included IL-18, IL-1, MIP-1 and MIP-2, whereas insulin, TIMP-1, GCP-2 and MPO emerged as late markers. Conclusions: Our data support the existence of a tight relationship between adipose tissue dysfunction and NASH pathogenesis and point to several novel potential predictive biomarkers for NASH.
Adipose tissue dysfunction signals progression of hepatic steatosis towards nonalcoholic steatohepatitis in C57BL/6 mice.
Specimen part
View SamplesPulmonary Hypertension (PH) is a frequent complication of Pulmonary Fibrosis (PF). PH can be seen in PF in the abscence of hypoxemia, irrespective of the degree of fibrosis. At the same time, a consistent number of patients with advanced PF never develop PH. The pathogenesis of PH secondary to PF remains unclear. PF patients are often referred to lung transplantation, but they present a higher incidence of pimary graft dysfunction than other diseases. The cause of this is unknown, and the relationship with PH remains unclear.
Gene expression profiling in the lungs of patients with pulmonary hypertension associated with pulmonary fibrosis.
Specimen part, Disease, Disease stage
View SamplesPancreatic cancer is characterized by heavy desmoplasia. Triptolide and its water-soluble pro-drug Minnelide are extremely efficient against pancreatic cancer in animal models. However, the effects of triptolide on pancreatic cancer stromal cells are largely unknown. The aim of this project is to indentify potential cellular functions that are affected by triptolide in pancreatic cancer associated fibroblasts. Overall design: Cancer associated fibroblasts were isolated from pancreatic tumor of KPC mouse model. Cells were either untreated or treated with 100nM triptolide for 6h or 24h before RNA isolation. The RNA was quality tested using a Bioanalyzer 2100 (Agilent Technologies, CA, USA). cDNA was created by reverse transcription of oligo-dT purified polyadenylated RNA and fragmented, blunt-ended, and then ligated to barcoded adaptors. Then, the library was size selected, and the selection process was validated and quantified by capillary electrophoresis and qPCR, respectively. Samples were load on the HiSeq 2500 (Illumina Inc., CA, USA) to generate around 25 million paired-end 50bp reads for each sample.
Inactivation of Cancer-Associated-Fibroblasts Disrupts Oncogenic Signaling in Pancreatic Cancer Cells and Promotes Its Regression.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Structural, functional and molecular analysis of the effects of aging in the small intestine and colon of C57BL/6J mice.
Sex, Age, Specimen part
View SamplesBy regulating digestion and absorption of nutrients and providing a barrier against the external environment the intestine provides a crucial contribution to the maintenance of health. To what extent aging-related changes in the intestinal system contribute to the impaired health of the aging body is still under debate. Young (4 months) and old (21 months) male C57BL/6J mice were fed a control low-fat (10E%) or a high-fat diet (45E%) for 2 weeks. During the intervention gross energy intake and energy excretion in the feces were measured. After sacrifice the small and large intestine were isolated whereby the small intestine was divided in three equal parts. Of each of the isolated segments Swiss rolls were prepared for histological analysis and the luminal content was isolated to examine alterations in the microflora with 16S rRNA Q-PCR. Furthermore, mucosal scrapings were isolated from each segment to determine differential gene expression by microarray analysis and global DNA methylation by pyrosequencing. Digestible energy intake was similar between the two age groups on both the control and the high-fat diet implying that macronutrient metabolism is not affected in 21-month-old mice. This observation was supported by the fact that the microarray analysis on RNA from intestinal scrapings showed no marked changes in expression of genes involved in metabolic processes. Decreased expression of Cubilin was observed in the intestine of 21-month-old mice, which might contribute to aging-induced vitamin B12 deficiency. Furthermore, microarray data analysis revealed enhanced expression of a high number of genes involved in immune response and inflammation in the colon, but not in the small intestine of the 21-month-old mice. Aging-induced global hypomethylation was observed in the colon and the distal part of the small intestine, but not in the first two sections of the small intestine. In 21-month old mice the most pronounced effects of aging was observed in the colon, limited changes were observed in the small intestine.
Structural, functional and molecular analysis of the effects of aging in the small intestine and colon of C57BL/6J mice.
Sex, Age, Specimen part
View Samples