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Homo sapiens
298 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
The use of microbiological cultures for diagnosing bacterial infections in young febrile infants have substantial limitations, including false positive and false negative cultures, and non-ideal turn-around times. Analysis of host genomic expression patterns (RNA biosignatures) in response to the presence of specific pathogens, however, may provide an alternate and potentially improved diagnostic approach. This study was designed to define bacterial and non-bacterial RNA biosignatures to distinguish these infections in young febrile infants.
Publication Title
Association of RNA Biosignatures With Bacterial Infections in Febrile Infants Aged 60 Days or Younger.
Sample Metadata Fields
Sex, Age, Specimen part, Race
View Samples- Danio rerio
- 6 Downloadable Samples
- Zebrafish Gene 1.0 ST Array (zebgene10st)
Description
Microcystin-LR (MC-LR), the most toxic member of microcystin family, inhibits protein phosphatase PP2A, triggers oxidative stress and induces hepatotoxicity. Gene expression profiling of MC-LR treated larvae using DNA microarray analysis revealed effects in the retinal visual cycle and pigmentation synthesis pathways that have not been previously associated with MC-LR. Liver-related genes were also differentially expressed. The microarray data were confirmed by quantitative real-time PCR. Our findings provide new evidence that microcystin-LR exposure of zebrafish larvae modulates the retinal visual cycle and pigmentation synthesis pathways and ultimately alter larval zebrafish behavior
Publication Title
Transcriptional and Behavioral Responses of Zebrafish Larvae to Microcystin-LR Exposure.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 5 Downloadable Samples
- Zebrafish Gene 1.0 ST Array (zebgene10st)
Description
We have characterised the zebrafish ortholog, setb, and investigated its role in embryogenesis. Phylogenetic analysis showed that zebrafish Setb has an amino acid sequence identity of approximately 96% with the mammalian orthologs. Whole mount immunofluorescence analysis revealed that Setb is expressed mainly in the eye, the lateral line neuromasts and the olfactory pit. Knockdown of setb using antisense morpholino oligonucleotides resulted in increased apoptosis, reduced cell proliferation and severe morphological defects. The morphant phenotypes were partially rescued when setb MO1 was co-injected with human set mRNA. In vivo labelling of hair cells in the lateral line of setb morphants with the vital fluorescent dye FM1-43 showed a significant decreased number of functional neuromasts. Gene expression analysis of setb morphants, employing DNA microarrays revealed a role of Setb in neurogenesis and the mechanosensory lateral line system.
Publication Title
The zebrafish homologs of SET/I2PP2A oncoprotein: expression patterns and insights into their physiological roles during development.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 28 Downloadable Samples
Illumina HiSeq 2500
Description
Right ventricular dysfunction (RVD) independently predicts worse outcomes in both heart failure (HF) and pulmonary hypertension (PH), irrespective of their etiologies. Yet no evidence-based therapies exist for RVD and progression towards RV failure (RVF) can occur in spite of optimal medical treatment of HF or PH. This disparity reflects our insufficient understanding of the molecular pathophysiology of RVF. To identify molecular mechanisms that may uniquely underlie RVF, we investigated the cardiac ventricular transcriptome of advanced HF patients, with and without RVF. Using weighted gene co-expression network and module-phenotype analyses, we identified a 279-member gene module that correlated significantly and specifically with RVF. Within this module, WIPI1 served as a genetic hub, HSPB6, SNAP47, and MAP4 as drivers, and PRDX5 as a repressor of RVF. We subsequently confirmed the ventricular specificity and temporal relationship of Wipi1, Hspb6, and Map4 transcript expression changes in murine models of pressure overload induced RV failure versus LV failure and subsequently uncovered differential dysregulation of autophagy in the failing RV versus the failing LV, namely a shift towards excessive non-canonical, Beclin1-independent, Wipi1/LC3II-mediated autophagy in RVF. In vitro siRNA silencing of Wipi1 partially protected isolated neonatal rat ventricular cardiac myocytes against aldosterone-induced failing phenotype. Moreover, silencing Wipi1 blunted mitochondrial superoxide production and limited non-canonical autophagy in this in vitro RVF model. Our findings suggest that Wipi1 regulates mitochondrial oxidative signaling and autophagy in cardiac myocytes. Inhibition of Wipi1 may hold promise as a therapeutic target for RVF. Overall design: Examination of RNAseq results from Left and Right Ventricles of 15 individuals, 5 control, 5 left-sided Heart Failure, 5 bi-ventricular Heart Failure
Publication Title
WIPI1 is a conserved mediator of right ventricular failure.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HiSeq 2500
Description
Phospholamban R14del mutazion (PLN-R14del) has been identified in a large family pedigree in which heterozygous carriers exhibited inherited dilated cardiomyopathy (DCM) and death by middle age. To better understand the causal link between the mutations in PLN and DCM pathology, we derived induced pluripotent stem cells from a DCM patient carrying the PLN R14del mutation. We showed that iPSC-derived cardiomyocytes recapitulated the DCM-specific phenotype and demonstrated that either TALEN-mediated genetic correction or combinatorial gene therapy resulted in phenotypic rescue. Our findings offer novel insights into the pathogenesis caused by mutant PLN and point to the development of potential new therapeutics of pathogenic genetic variants associated with inherited cardiomyopathies. Overall design: iPSCs were derived from a female patient carrying a heterozygous mutation (R14del) in the PLN gene. Tree samples were analyzed: Cardiomyocytes derived from PLN-R41del iPSC cells (R14del-CM); R14del-CMs infected with AAV6-EGFP-miR-PLN and R14del-CMs infected with AAV6-EGFP-miR-luc used as a negative control
Publication Title
Correction of human phospholamban R14del mutation associated with cardiomyopathy using targeted nucleases and combination therapy.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Hox genes are required for the development of the intestinal caecum, a major organ of species eating plants. We have analysed the transcriptional regulation of Hoxd genes in caecal buds and show that they are controlled by a series of enhancers located in a gene desert telomeric to the HoxD cluster. The start site of two neighboring and opposite long non-coding RNAs, Hotdog and Twin of Hotdog, specifically transcribed in the caecum, contacts the expressed Hoxd genes in the framework of a topological domain, a large domain of interactions, which ensures a robust transcription of these genes during caecum budding. We show that hedgehogs have kept this regulatory potential despite the absence of caecum, suggesting that these enhancers are used in other developmental situations. In this context, we discuss some striking similarities between the caecum and the limb buds, suggesting the implementation of a common budding tool-kit. Overall design: Transcriptional activity at the HoxD locus in the murine developing gut at E13, Differential gene expression analysis along the murine developing gut
Publication Title
Multiple enhancers regulate Hoxd genes and the Hotdog LncRNA during cecum budding.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples
SRP018708- Mus musculus
- 1 Downloadable Sample
- Illumina Genome Analyzer II
Description
Hox genes are required for the development of the intestinal caecum, a major organ of species eating plants. We have analysed the transcriptional regulation of Hoxd genes in caecal buds and show that they are controlled by a series of enhancers located in a gene desert telomeric to the HoxD cluster. The start site of two neighboring and opposite long non-coding RNAs, Hotdog and Twin of Hotdog, specifically transcribed in the caecum, contacts the expressed Hoxd genes in the framework of a topological domain, a large domain of interactions, which ensures a robust transcription of these genes during caecum budding. We show that hedgehogs have kept this regulatory potential despite the absence of caecum, suggesting that these enhancers are used in other developmental situations. In this context, we discuss some striking similarities between the caecum and the limb buds, suggesting the implementation of a common budding tool-kit. Transcriptional activity at the HoxD locus in developing caeca at E13.5 Overall design: Transcriptional activity at the HoxD locus in developing caeca at E13.5
Publication Title
Multiple enhancers regulate Hoxd genes and the Hotdog LncRNA during cecum budding.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Pseudomonas aeruginosa
- 10 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
The Pseudomonas aeruginosa MvfR-dependent QS regulatory pathway controls the expression of key virulence genes; and is activated via the extracellular signals 4-hydroxy-2-heptylquinoline (HHQ) and 3,4-dihydroxy-2-heptylquinoline (PQS), whose syntheses depend on anthranilic acid (AA), the primary precursor of 4-hydroxy-2-alkylquinolines (HAQs). We identified halogenated AA analogs that specifically inhibited HAQ biosynthesis and disrupted MvfR-dependent gene expression. These compounds restricted P. aeruginosa systemic dissemination and mortality in mice, without perturbing bacterial viability, and inhibited osmoprotection, a widespread bacterial function.
Publication Title
Inhibitors of pathogen intercellular signals as selective anti-infective compounds.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 178 Downloadable Samples
- Illumina HiSeq 4000
Description
Human mononuclear phagocytes comprise phenotypically and functionally overlapping subsets of dendritic cells (DC) and monocytes, but their identification remains elusive. By integrating high-dimensional single-cell protein and RNA expression data, we clearly delineated monocytes from conventional DC2 (cDC2), identifying new markers including CD88/CD89 for monocytes and HLA-DQ/Fc?RI? for cDC2, allowing their unambiguous characterization in blood and tissues. We also show that cDC2 can be subdivided into phenotypically and functionally distinct subsets based on CD5, CD163 and CD14 expression, including a unique subset of circulating inflammatory CD5-CD163+CD14+ cells related to previously defined DC3. These inflammatory DC3 were expanded in systemic lupus erythematosus patients, correlating with disease activity. Unravelling the heterogeneity of DC sub-populations in health and disease paves the way for specific DC subset-targeting therapies. Overall design: Indexed single cell RNAseq (scRNAseq) of human peripheral blood dendritic cells and monocytes
Publication Title
Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples