Background and aims: Dysregulation of intestinal epithelial cells performance associates with an array of pathologies whose onset mechanisms are incompletely understood. The aim of the present study was to provide a map of gene expresssion patterns along the human healthy adult gastro-intestinal tract and to implement a new procedure for microarray data noise filtering that would allow their use as a reference when screening for pathological deviations, such as inflammatory bowel disease (IBD). Methods: Gene expression profiles in antrum, duodenum, jejunum, ileum and transverse colon biopsies were measured with the Affymetrix U133A array and principal component analysis was used to identify region-selective biomarkers. These data were intersected with highly variable genes from a public dataset of gene expression in the ileal and colonic healthy regions of UC and Crohns disease patients. Moreover, gene sets covering gut functions not entirely accounted for by the available public tools were constructed to monitor their expression along the GI tract. Results: 166 genes were found to be responsible for distinguishing the five regions considered. Fourteen had never been described in the GI tract, including a semaphorin probably implicated in pathogen invasion, and six other novel genes. Similar analysis of the IBD datasets revealed that samples stratify based on disease rather than on the intestinal region. This withstanding, eleven genes were identified as possible early predictors of Crohns and/or UC in ileum and/or colon. These include CLCA4 and SLC26A2, both implicated in ion transport. Conclusions: This novel approach, validated by retrieving known gene profiles, allowed the identification of promising new leads both in health and IBD state.
Biomarkers of human gastrointestinal tract regions.
Age
View SamplesOchratoxin A gene expression profiling in liver and kidney, with time points of exposure from 7 days to 12 motnhs
A toxicogenomics approach to identify new plausible epigenetic mechanisms of ochratoxin a carcinogenicity in rat.
No sample metadata fields
View SamplesThe discovery of activity-dependent neuroprotective protein (ADNP) regulated tooth eruption in mice and man, provides, for the first time, an early detection of tooth eruption, with full or almost full mouth of teeth at one year of age, as a potential biomarker for an intellectual disability (ID)/autism spectrum disorder (ASD) syndrome, toward improved translational medicine. Overall design: RNAseq of 4 samples, comparing three ADNP-mutated lymphoblastoid cell lines (LCLs, derived from ADNP-mutated children) with a non-mutated cell line. No replicates were performed but results were verified usign RT-PCR.
Tauopathy in the young autistic brain: novel biomarker and therapeutic target.
Specimen part, Cell line, Subject
View SamplesA key function of Na+/H+ exchanger regulatory factor 2 (NHERF2) is spatial organization of signaling proteins to facilitate signal transduction. The role of NHERF2 in cancer progress is not well understood. This study determines how loss of NHERF2 alter colon cancer progress. Overall design: We show that loss of NHERF2 decreases colon cancer cell proliferation. To compare the effects of NHERF2 and LPA2 at the molecular level, HCT116 colon cancer xenograft with knockdown of NHERF2 or LPA2 was analyzed by RNAseq. Please note that standard cufflinks/cuffdiff output files are provided in the compressed tar files as processed data and Cufflinks/Cuffdiff output file content/formats are described at: https://cole-trapnell-lab.github.io/cufflinks/cuffdiff/#cuffdiff-output-files https://cole-trapnell-lab.github.io/cufflinks/file_formats/ (also included in the ''readme.txt'' file)
Deletion of Na+/H+ exchanger regulatory factor 2 represses colon cancer progress by suppression of Stat3 and CD24.
No sample metadata fields
View SamplesThis series contain mouse and rat lung samples treated with mechanical ventilation and corresponded controls.
Bioinformatic identification of novel early stress response genes in rodent models of lung injury.
No sample metadata fields
View SamplesExperiments in rodents have shown that kidney ischemia/reperfusion injury (IRI) facilitates lung injury and inflammation. To identify potential ischemia-specific lung molecular pathways involved, we conducted global gene expression profiling of lung 6 or 36 hours following 1) bilateral kidney IRI, 2) bilateral nephrectomy (BNx), and 3) sham laparotomy in C57BL/6J mice. Total RNA from whole lung was isolated and hybridized to 430MOEA (22,626 genes) GeneChips (n=3/group).
Ischemic acute kidney injury induces a distant organ functional and genomic response distinguishable from bilateral nephrectomy.
No sample metadata fields
View SamplesDrosophila miRNAs show distinct change in isoform distribution pattern with age. Some miRNAs show accumulation of the short isoforms, while other miRNAs show the accumulation of the long isoforms with age. The increase of the long isoforms of some miRNAs reflects increased 2''-O-methylated miRNA isoforms with age. The increase in 2''-O-methylated miRNA isoforms reflected increased Ago2-loading, but not Ago1-loading of specific miRNA isoforms with age. This raised a question on whether there is global shift in small RNA loading pattern between Ago1 and Ago2 with age. To investigate change in small RNA loading pattern between Ago1 and Ago2 with age, we performed small RNA deep-sequencing of Ago1 vs Ago2-IP small RNAs at 3d and 30d in Drosophila. This analysis revealed global increase of miRNA loading into Ago2, but not into Ago1 with age. Overall design: 3d and 30d FLAG-HA-Ago2 male flies were collected. Ago1 and Ago2 were immunoprecipitated by anti-Ago1 and anti-FLAG M2 beads respectively. RNA was purified from the beads, P32-labeled, and small RNA fraction was gel-purififed. Small RNA libraries were prepared using Illumina''s TruSeq small RNA sample preparation kit (#RS-200-0012, Illumina, Inc. San Diego, CA), following the manufacturer''s protocol. The libraries were multiplexed and sequenced on HiSeq2000 platform (Illumina).
Impact of age-associated increase in 2'-O-methylation of miRNAs on aging and neurodegeneration in Drosophila.
Sex, Specimen part, Subject
View SamplesWe examined early and late gene expression changes using the IT LPS model of Acute Lung Injury (ALI). In this model, injury peaks at day 4 and is almost completely resolved by day 10 in wild type (WT) C57BL/6 mice. In contrast to the pattern in WT mice, lymphocyte-deficient Rag-1 -/- mice exhibit strikingly delayed resolution despite similar initial injury.
Regulatory T cell-mediated resolution of lung injury: identification of potential target genes via expression profiling.
Sex, Specimen part, Treatment, Time
View SamplesObstructive sleep apnea (OSA) leads to increased cardiovascular morbidity and mortality, which have been attributed to intermittent hypoxia (IH). The effects of IH on lung structure and function are unknown. We used a mouse model of chronic IH, which mimics the O2 profile in patients with OSA. We exposed adult C57BL/6J mice to 3 months of IH with an FIO2 nadir of 5%, 60 times/hr during the 12hr light phase. Control mice were exposed to room air.
Chronic intermittent hypoxia induces lung growth in adult mice.
Sex, Specimen part
View SamplesOsteosarcoma (OS) is the malignant bone tumor with a high tendency to metastasize to the lung, where the molecular mechanisms are unclear. The mouse OS cell line LM8 has been isolated originally from the Dunn OS cell line by in vivo selection as a subline with a high metastatic potential to the lung.
Stable knockdown of S100A4 suppresses cell migration and metastasis of osteosarcoma.
Cell line
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