Critically ill preterm infants experience multiple stressors while hospitalized. Morphine is commonly prescribed to ameliorate their pain and stress. We hypothesized that neonatal stress will have a dose-dependent effect on hippocampal gene expression, and these effects will be altered by morphine treatment. Male C57BL/6 mice were exposed to 5 treatment conditions between postnatal day 5 and 9: 1) Control, 2) mild stress + saline, 3) mild stress + morphine, 4) severe stress + saline and 5) severe stress + morphine. Hippocampal RNA was extracted and analyzed using Affymetrix Mouse Gene 1.0 ST Arrays. Single gene analysis and gene set analysis were used to compare groups with validation by qPCR. Stress resulted in enrichment of genes sets related to fear response, oxygen carrying capacity and NMDA receptor synthesis. Morphine downregulated gene sets related to immune function. Stress plus morphine resulted in enrichment of mitochondrial electron transport gene sets, and down-regulation of gene sets related to brain development and growth. We conclude that neonatal stress alone influences hippocampal gene expression, morphine alters a subset of stress-related changes in gene expression and influences other gene sets. Stress plus morphine show interaction effects not present with either stimulus alone. These changes may alter neurodevelopment.
Effects of neonatal stress and morphine on murine hippocampal gene expression.
Sex, Specimen part, Treatment
View SamplesMost of the breast cancer samples used in clinical research contain multiple cell types other than epithelial cells alone. The non-epithelial cell types have have a substantial effect on the gene expression-profile, which is used to define molecular subtypes of the tumours. The purpose of this data set is to retrieve gene-expression profile within tumour epithelial cells. We collected 9 breast cancer epithelial cell lines and 5 tumour sampes from which epithelial cells were sorted and enriched using BerEp4 antibody coated beads. We profiled the mRNA expression level of these samples and classified probe sets into epithelial genes which were those genes with present calls in at least 50% of the samples. Then we derived an 23-gene signature based on only the epithelial genes to stratify breast cancer.
Minimising immunohistochemical false negative ER classification using a complementary 23 gene expression signature of ER status.
Specimen part
View SamplesIn humans, the most common sex chromosomal disorder is Klinefelter syndrome (KS), caused by the presence of one or more extra X-chromosomes. The KS patients display a diverse adult phenotype with increased height, gynaecomastia, and hypergonadotropic hypogonadism as the most common symptoms. Men with KS are almost always infertile due to testicular degeneration, which accelerates during puberty. Very few studies investigated when the germ cell loss begins and whether it is caused by dysgenetic fetal development of the testes. We investigated a series of fetal KS testis tissue samples and found a marked reduction in MAGE-A4-positive pre-spermatogonia in the developing KS gonads compared to controls, indicating a failure of the gonocytes to differentiate into pre-spermatogonia. Transcriptome analysis by RNA sequencing of formalin-fixed and paraffin embedded gonads originating from 4 fetal KS samples and 5 age- and cellularity-matched controls revealed 211 differentially expressed transcripts in the fetal KS testis. We found a significant enrichment of upregulated X-chromosomal transcripts and validated the expression of the pseudoautosomal region 1 (PAR1) gene, AKAP17A. Moreover, we found enrichment of long non-coding RNAs in the KS testes (e.g. LINC01569 and RP11-485F13.1). In conclusion, our data indicates that the testicular phenotype observed among adult men with KS is initiated already in fetal life by failure of the gonocyte differentiation into pre-spermatogonia, which could be due to aberrant expression of long non-coding RNAs. Overall design: Includes a total of 9 samples. 4 fetal Klinefelter and 5 age-matched controls testis samples
Transcriptome profiling of fetal Klinefelter testis tissue reveals a possible involvement of long non-coding RNAs in gonocyte maturation.
Subject
View SamplesBackground: Avian infectious bronchitis (IB) is an acute and highly contagious disease of the upper-respiratory tract caused by infectious bronchitis virus (IBV). Understanding the molecular mechanisms involved in the interaction between innate and adaptive immune responses to IBV infection is a crucial element for further improvements in strategies to control IB. To this end, two chicken lines, selected for high and low serum concentration of mannose-binding lectin (MBL), a soluble pattern recognition receptor, were studied. In total, 32 birds from each line (designated L10H for high and L10L for low MBL serum concentration, respectively) were used. Sixteen birds from each line were infected with IBV at 3 weeks of age and sixteen birds were left uninfected. Eight uninfected and eight infected birds from each line were euthanized at 1 and 3 weeks post infection. RNA sequencing was performed on spleen samples from all 64 birds used in the experiment. Differential gene expression analysis was performed for four comparisons: L10L line versus L10H line for uninfected birds at weeks 1 and 3, respectively, and L10L line versus L10H line for infected birds at weeks 1 and 3, respectively. Functional analysis based on the differentially expressed genes was performed using Gene Ontology (GO) Immune System Process terms specific for Gallus gallus. Results: Comparing uninfected L10H and L10L birds, we identified 1698 and 1424 differentially expressed (DE) genes at weeks 1 and 3, respectively. For the IBV-infected birds, 1934 and 866 DE genes were identified between the two lines at weeks 1 and 3, respectively. In both cases DE genes had FDR-adjusted p-value <0.05. The two most enriched GO terms emerging from the comparison of uninfected birds between the two lines were “Lymphocyte activation involved in immune response” (GO:0002285) and “Somatic recombination of immunoglobulin genes involved in immune response” (GO:0002204) at weeks 1 and 3, respectively. When comparing IBV-infected birds between the two lines, the most enriched GO terms were “Alpha-beta T cell activation” (GO:0046631) and “Positive regulation of leukocyte activation” (GO:0002696) at weeks 1 and 3, respectively. Conclusion: Healthy birds from the two lines showed significant differences in expression profiles for subsets of both adaptive and innate immunity-related genes, whereas comparison of the IBV-infected birds from the two lines showed differences in expression of immunity-related genes involved in T cell activation and proliferation. The observed transcriptome differences between the two lines indicate that selection for MBL had a much wider effect than solely on serum MBL concentration, and in addition influenced the innate and adaptive immune responses. Future research will focus on identifying signatures of selection in order to further understand molecular pathways be responsible for differences between the two lines as well as for efficient IBV immune protection. Overall design: For this study 64 spleen samples were harvested and used for RNA sequencing from birds originating from the two Aarhus University inbred lines, L10H and L10L. The birds were infected at age of 3 weeks and they were sacrificed 1 and 3 weeks post infection by cervical dislocation and spleen samples were collected. At both time points, eight samples from the two lines, L10H and line L10L, from each group (uninfected and infected) were collected.
RNA sequencing-based analysis of the spleen transcriptome following infectious bronchitis virus infection of chickens selected for different mannose-binding lectin serum concentrations.
Specimen part, Subject, Time
View SamplesIn humans, the most common sex chromosomal disorder is Klinefelter syndrome (KS), caused by the presence of one or more extra X-chromosomes. The KS patients display a diverse adult phenotype with increased height, gynaecomastia, and hypergonadotropic hypogonadism as the most common symptoms. Men with KS are almost always infertile due to testicular degeneration, which accelerates during puberty. Very few studies investigated the global gene expression analysis of adult KS testes and, more importantly, which cell types the differentially expressed transcripts originate from. Transcriptome analysis by RNA sequencing of fixed and paraffin embedded testes originating from 3 adult KS samples and 3 adult cellularity-matched controls revealed 236 differentially expressed transcripts in the adult KS testis. To examine the cellular origin of the differentially expressed transcripts, transcriptome profiling was also carried out on 4 testes with Sertoli Cell-Only and 4 testes with full spermatogenesis. Also, pre-pubertal KS and controls were RNA-sequenced. Overall design: Includes a total of 22 testis samples. 3 adult Klinefelter, 3 Klinefelter-like, 4 Sertoli Cell-Only, 4 with full spermatogenesi, 4 pre-pubertal Klinefelter and 4 pre-pubertal controls
Transcriptome analysis of the adult human Klinefelter testis and cellularity-matched controls reveals disturbed differentiation of Sertoli- and Leydig cells.
Specimen part, Subject
View SamplesEvidence suggests that BRCA1 mutation associated tumors have increased sensitivity to DNA damaging agents like cisplatin. Sporadic triple negative breast cancers (TNBC) have many phenotypic similarities to BRCA1 tumors and may have a similar sensitivity to cisplatin. We tested the efficacy of cisplatin monotherapy in 28 TNBC patients in a single arm neoadjuvant trial with outcome measured by pathologic treatment response quantified using the Miller-Payne scale.
Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer.
Age, Disease stage
View SamplesThe study aimed to resolve the mechanisms of protective actions of MMP-8 in oral tongue squamous cell carcinoma.
The interplay of matrix metalloproteinase-8, transforming growth factor-β1 and vascular endothelial growth factor-C cooperatively contributes to the aggressiveness of oral tongue squamous cell carcinoma.
No sample metadata fields
View SamplesThe composition of the matrix molecules is important in in vitro cell culture experiments of e.g. human cancer invasion and vessel formation. Currently, the mouse Engelbreth-Holm-Swarm (EHS) sarcoma -derived products, such as Matrigel, are the most commonly used tumor microenvironment mimicking (TMEM) matrices for experimental studies. However, since Matrigel is non-human in origin, its molecular composition does not accurately simulate human TMEM and we expect myogel to be more natural environment for human cancer cells. The environment may have crucial impact on cell behavior and gene expression.
A novel human leiomyoma tissue derived matrix for cell culture studies.
Cell line
View Samples