Host-microbe associations underlie many key processes of host development, immunity, and life history. Yet, none of the current research on the central model species Caenorhabditis elegans considers the worm's natural microbiome. Instead, almost all laboratories exclusively use the canonical strain N2 and derived mutants, maintained through routine bleach sterilization in monoxenic cultures with an E. coli strain as food. Here, we characterize for the first time the native microbiome of C. elegans and assess its influence on nematode life history characteristics via transcriptomics. Overall design: mRNA profiles of wild type (WT) C.elegans fed to either Ochrobactrum strain MYb65, MYb71, mixture of MYb65 and MYb71 or standard lab food E. coli OP50 at different life stages (from L2 to adults) were generated by deep sequencing, in triplicate, using Illumina HiSeq2000.
The Inducible Response of the Nematode <i>Caenorhabditis elegans</i> to Members of Its Natural Microbiota Across Development and Adult Life.
Cell line, Treatment, Subject, Time
View SamplesWorms were treated with bcat-1 RNAi Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de) Overall design: 6 samples: 3 replicates for bcat-1 RNAi treatment; 3 replicates for controls
Branched-chain amino acid catabolism is a conserved regulator of physiological ageing.
Cell line, Subject
View SamplesMultiple signaling pathways, structural proteins and transcription factors are involved in regulation of endothelial barrier function. The Forkhead protein FOXF1 is a key transcriptional regulator of lung embryonic development, and we use a conditional knockout approach to examine the role of FOXF1 in adult lung homeostasis and lung injury and repair. Tamoxifen-regulated deletion of both Foxf1 alleles in endothelial cells of adult mice (Pdgfb-iCreER/Foxf1 caused lung inflammation and edema, leading to respiratory insuffency and uniform mortality. Deletion of a single foxf1 allele was sufficient to increase susceptibility of heterozygous mice to acute lung injury. FOXF1 abundance was decreased in pulmonary endothelial cells of human patients with acute lung injury. Gene expression analysis of pulmonary endothelial cells of FOXF1 deletion indicated reduced expression for genes critical for maintance and regulation of adherens junctions. FOXF1 knockdown in vitro and in vivo disrupted adherens junctions, increased lung endothelial permeability, and the abundance of mRNA and protein for sphingosine 1 phosphate receptor 1 (S1PR1), a key regulator of endothelial barrier function. Chromatin immunoprecipitation and luciferase reporter assay demonstrated that FOXF1 directly bound to and induced the tanscriptional activity of the S1pr1 promoter. Pharmacological administratiion of S1P to injured pdgfb-iCreER/Foxf1 mice restored endothelial barrier function, decreased lung edema and improved survival. Thus, FOXF1 promotes normal lung homeostasis and lung repair, at least in part, by enhancing endothelial barrier function through transcriptional activation of the S1P/S1PR1/ signaling pathway. Overall design: RNA was isolated and pooled from the lungs of multiple mice with either the Foxf1 floxed alleles alone or Pdgfb-iCreER Foxf1 floxed mice.
FOXF1 maintains endothelial barrier function and prevents edema after lung injury.
Specimen part, Subject
View SamplesMyotonic dystrophy type 1 (DM1) is a dominantly inherited disease that affects multiple organ systems. Cardiac dysfunction is the second leading cause of death in DM1. We quantified gene expression in heart tissue from a heart-specific DM1 mouse model (EpA960/MCM) which inducibly expresses human DMPK exon 15 containing 960 CUG expanded repeats and that reproduced Celf1 up regulation. To assess if, in addition to splicing and miRNA defects, CUGexp RNA also perturbed the steady state mRNA levels of genes, we carried out a microarray study on wildtype E14, adult, MCM controls and DM1 mouse hearts. As anticipated we noted a large number of genes to be developmentally regulated in wildtype hearts, however, within 72h of induction of CUGexp RNA there appeared to be a coordinate adult-to-embryonic shift in steady state levels of many genes.
The Mef2 transcription network is disrupted in myotonic dystrophy heart tissue, dramatically altering miRNA and mRNA expression.
Specimen part, Time
View SamplesReduction in the cellular levels of the cyclin kinase inhibitor p27kip1 are frequently found in many human cancers and correlate directly with patient prognosis. Specifically ubiquitin dependent proteasomal turnover has been shown to cause reduced p27 expression in many human cancers. We recently demonstated that expression of a stabilized version of p27kip1 (p27kip1T187A) in a genetically modified mouse significantly reduced the number of intestinal adenomatous polyps which progressed to invasive carcinomas. Based on this work we set out to identify compounds which lead to a re-expression of p27 in cancer tissues. In this work we identify Argyrin A a compound derived from myxobacterium archangium gephyra as a potent inducer of p27kip1 expression. Argyrin A induces apoptosis in human colon cancer xenografts and tumor vasculature in vivo leading to a profound reduction in tumor size at well tolerated levels. Argyrin A functions are strictly dependent on the expression of p27kip1 as neither tumor cells nor endothelial cells which do not express p27kip1 respond to this compound. Surprisingly the molecular mechanism by which Argyrin A exerts its p27 dependent biological function is through a potent inhibition of the 20S proteasome.
Argyrin a reveals a critical role for the tumor suppressor protein p27(kip1) in mediating antitumor activities in response to proteasome inhibition.
Specimen part
View SamplesComparison of temporal gene expression profiles Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de) Overall design: 115 samples in sum; 5 age groups (2, 9, 15, 24, 30 months); 4 tissues (brain, liver, skin, blood); 5-8 samples per group
Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderly.
Specimen part, Cell line, Subject
View SamplesComparison of temporal gene expression profiles Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de) Overall design: 75 samples in sum; 5 age groups (6, 12, 24, 36, 42 months); 3 tissues (brain, liver, skin); 5 samples per group
Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderly.
No sample metadata fields
View SamplesBroilers were immunized with three variants of subunit vaccines, based on the hemagglutinin (HA) DNA and Pichia-produced HA protein from H5N1 virus, in comparison to the control group, which was administered an empty vector (pCI). Gene expression changes in the spleens of chickens were investigated at 7 day post booster dose.
Transcriptional response to a prime/boost vaccination of chickens with three vaccine variants based on HA DNA and Pichia-produced HA protein.
Specimen part, Treatment
View SamplesThere is cardiac dysfunction in male eNOS (-/-) with age and 50% mortality at 21M. It was of interest to investigate the gene expression profile of aged eNOS (-/-) male in comparison to (+/+) in order to explore the genetic markers and molecular mechanisms leading to heart failure. RNA was extracted from the left ventricle from male (-/-) (n=3) and (+/+) (n=4) at the age of 21M.
Transcriptional basis for exercise limitation in male eNOS-knockout mice with age: heart failure and the fetal phenotype.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Response to a DNA vaccine against the H5N1 virus depending on the chicken line and number of doses.
Specimen part, Treatment
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