Transcriptome analyses of organ transplants have until now usually focused on whole tissue samples containing activation profiles from different cell populations. Here, we enriched endothelial cells from rat cardiac allografts and isografts, establishing their activation profile at baseline and on day 2, 3 and 4 after transplantation. Modulated transcripts were assigned to three categories based on their regulation profile in allografts and isografts. Categories A and B contained the majority of transcripts and showed similar regulation in both graft types, appearing to represent responses to surgical trauma. By contrast, category C contained transcripts that were partly allograft-specific and to a large extent associated with interferon-gamma-responsiveness. Several transcripts were verified by immunohistochemical analysis of graft lesions, among them the matricellular protein periostin which was one of the most highly upregulated transcripts but has not been associated with transplantation previously. In conclusion, the majority of the differentially expressed genes in graft endothelial cells are affected by the transplantation procedure whereas relatively few are associated with allograft rejection.
Genome-wide transcription profile of endothelial cells after cardiac transplantation in the rat.
Sex, Specimen part
View SamplesThe inflammatory response initiated by microbial products signaling through Toll-like receptors (TLRs) of the innate immune system is essential for host defense against infection. Because inflammation can be harmful to host tissues, the innate response is highly regulated. Negative regulation of TLR4, the receptor for bacterial lipopolysaccharide (LPS), results in LPS tolerance, defined as hyporesponsiveness to repeated stimulation with LPS. LPS tolerance is thought to protect the host from excessive inflammation by turning off TLR4 signal, which then shuts down TLR-induced genes. However, TLR signaling induces hundreds of genes with very different functions. We reasoned that genes with different functions should have different requirements for regulation. Specifically, genes encoding proinflammatory mediators should be transiently inactivated to limit tissue damage, while genes encoding antimicrobial effectors, which directly target pathogens, should remain inducible in tolerant cells to protect the host from infection. Using an in vitro system of LPS tolerance in macrophages, here we show that TLR-induced genes may indeed be divided into two distinct categories based on their functions and regulatory requirements. Further, we show these distinct groups are regulated by gene-specific, and not signal-specific mechanisms.
Gene-specific control of inflammation by TLR-induced chromatin modifications.
Specimen part
View SamplesThis study focused on transcription in the medial PFC (mPFC) as a function of age and cognition. Young and aged F344 rats were characterized on tasks, attentional set shift and spatial memory, which depend on the mPFC and hippocampus, respectively. Differences in transcription associated with age and cognitive function were examined using RNA sequencing to construct transcriptomic profiles for the mPFC, white matter, and region CA1 of the hippocampus. The results indicate regional differences in vulnerability to aging associated with increased expression of immune and defense response genes and a decline in synaptic and neural activity genes. Importantly, we provide evidence for region specific transcription related to behavior. In particular, expression of transcriptional regulators and neural activity-related immediate-early genes (IEGs) are increased in the mPFC of aged animals that exhibit delayed set shift behavior; relative to age-matched animals that exhibit set shift behavior similar to younger animals. Overall design: The study contains 11 young and 20 aged rats for the mPFC and CA1 samples, which were used to investigate expression patterns associated with aging and behavior. White matter samples were used to investigate an age-related effect with 8 young and 9 aged rats.
Transcription Profile of Aging and Cognition-Related Genes in the Medial Prefrontal Cortex.
No sample metadata fields
View SamplesAging is associated with a decline in hippocampal mediated learning and memory, a process wich can be ameliorated by dietary (caloric) restriction. We used Affymetrix gene expression analysis to monitor changes in three regions of the hippocampus (CA1, CA3, DG) of middle aged (18 months) and old (28 month) rats that were exposed to dietary restriction. Old rats were determined to be good performers (GP) or poor performers (PP) in behavioral tests to assess thier hippocampal function.
Gene expression in the hippocampus: regionally specific effects of aging and caloric restriction.
Age, Specimen part
View SamplesISCOM vaccines induce a balanced Th1/Th2 response and cytotoxic T lymphocytes. The adjuvant component, ISCOM-Matrix, consists of purified saponin fractions, cholesterol and phospholipids. The mode of action for the ISCOM-Matrix is known to some extent but still we lack knowledge of important segments in initiation of the immune response. The study was performed to analyze the early transcriptional responses to the ISCOM-Matrix alone, without the use of co-administered antigen. Matrix M (AbISCO 100) was given as intramuscular injection and after 24 hours the pigs was sacrificed for gene expression analysis, performed for the injection site and the draining lymph node.
Global transcriptional response to ISCOM-Matrix adjuvant at the site of administration and in the draining lymph node early after intramuscular injection in pigs.
Sex, Age, Specimen part, Treatment
View SamplesCancer-related fatigue is one of the most frequent complaints among breast cancer survivors, with a major negative impact on general life. However, the etiology behind this syndrome is still unraveled. Gene expression analysis was performed on whole blood samples from breast cancer survivors classified as either fatigued or non-fatigued at two consecutive time points. The analysis identified several gene sets concerning plasma and B cell pathways as different between the fatigue and non-fatigue groups, suggesting that a deregulation in these pathways might underlie the fatigue syndrome. The fatigue group also showed a higher mean level of leucocytes, lymphocytes and neutrophiles compared with the non-fatigue group, thus further implicating the immune system in the biology behind the fatigue syndrome.
Alterations of gene expression in blood cells associated with chronic fatigue in breast cancer survivors.
Specimen part, Subject
View SamplesCell body and pseudopod RNA are differentially regulated during the migration of the metastatic cancer cells.We wanted to identify the RNA which are upregulated in the pseudopodial (PS) fraction as compared to cell body fraction (CB).
Pseudopodial actin dynamics control epithelial-mesenchymal transition in metastatic cancer cells.
Cell line
View SamplesThe Atss3 mutant and WT plants were arranged according to a Randomized Complete Block Design. The plants were planted in rows with seven rows in each flat; two plants of the same genotype/pot. Plants were grown under a SD photoperiod (8 h light/16 h dark) in a growth chamber as described. Eight randomly selected rows were harvested for each time point from different flats. Plant material was harvested at five time points in the diurnal cycle (1, 4, 8.5, 12, and 16 h; Time 0 is the beginning of the light period); harvesting was conducted under a green safety light. Each sample consisted of rosette leaves (leaves 5 to 8, staged following Bowmann (1994); photosynthetically active (Stessman et al., 2002)) from sixteen six-week-old plants. Leaf samples were frozen in liquid N2 immediately after harvest and stored at -80C for RNA extraction. The experiment was done twice and independent randomizations for plant growth and harvest were used for the two replicates.
Identification of the novel protein QQS as a component of the starch metabolic network in Arabidopsis leaves.
No sample metadata fields
View SamplesLeukotriene E4 (LTE4) the most stable of the cysteinyl leukotrienes (cysLTs) binds poorly to classical type 1 (CysLT1) and 2 (CysLT2) receptors although it induces potent responses in human airways in vivo, such as bronchoconstriction, airway hyperresponsiveness and inflammatory cell influx suggesting the presence of a novel receptor that preferentially responds to LTE4. To identify such a receptor two human mast cell lines, LAD2 and LUVA, were selected that differentially responded to LTE4 when analysed by intracellular signalling and gene expression. Comparative transcriptome analysis and recombinant gene overexpression experiments revealed CysLT1 as a receptor responsible for potent LTE4-induced response in LAD2 but not in LUVA cells, an observation confirmed further by gene knockdown and selective inhibitors. Lentiviral overexpression of CysLT1 in LUVA cells augmented intracellular calcium signalling induced by LTE4 but did not restore full agonist responses at the gene expression level. Our data support a model where both an increased expression of Gq-coupled CysLT1, and sustained intracellular calcium mobilisation and extracellular signal-regulated kinase (Erk) activation, are required for LTE4-mediated regulation of gene expression in human cells. Our study shows for the first time that CysLT1 expression is critically important for responsiveness to LTE4 within a human cell system.
Leukotriene E4 is a full functional agonist for human cysteinyl leukotriene type 1 receptor-dependent gene expression.
Cell line
View SamplesNormal human tissue samples from ten post-mortem donors were processed to generate total RNA, which was subsequently analyzed for gene expression using Affymetrix U133 plus 2.0 arrays. Donor information: Donor 1 - 25 year old male; donor 2 - 38 year old male; donor 3 - 39 year old female; donor 4 - 30 year old male; donor 5 - 35 year old male; donor 6 - 52 year old male; donor 7 - 50 year old female; donor 8 - 48 year old female; donor 9 - 53 year old female; donor 10 - 23 year old female
Gene expression analyses reveal molecular relationships among 20 regions of the human CNS.
No sample metadata fields
View Samples