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SRP102487
Homo sapiens
16 Downloadable Samples
Illumina HiSeq 2000
Description
Idiopathic pulmonary fibrosis (IPF) is a progressive disease of the middle aged and elderly with a prevalence of one million persons worldwide. The fibrosis spreads from affected alveoli into contiguous alveoli, creating a reticular network that leads to death by asphyxiation. Lung fibroblasts from patients with IPF have phenotypic hallmarks, distinguishing them from their normal counterparts: pathologically activated Akt signaling axis, increased collagen and a-smooth muscle actin expression, distinct gene expression profile, and ability to form fibrotic lesions in model organisms. Despite the centrality of these fibroblasts in disease pathogenesis, their origin remains uncertain. Here, we report the identification of cells in the lungs of patients with IPF with the properties of mesenchymal progenitors. In contrast to progenitors isolated from nonfibrotic lungs, IPF mesenchymal progenitor cells produce daughter cells manifesting the full spectrum of IPF hallmarks, including the ability to form fibrotic lesions in zebrafish embryos and mouse lungs, and a transcriptional profile reflecting these properties. Morphological analysis of IPF lung tissue revealed that mesenchymal progenitor cells and cells with the characteristics of their progeny comprised the fibrotic reticulum. These data establish that the lungs of patients with IPF contain pathological mesenchymal progenitor cells that are cells of origin for fibrosis-mediating fibroblasts. These fibrogenic mesenchymal progenitors and their progeny represent an unexplored target for novel therapies to interdict fibrosis. Overall design: RNA-seq of lung fibroblasts from IPF or healthy control patients at day 0 or day 21 of culture.
Publication Title
Calcium-binding protein S100A4 confers mesenchymal progenitor cell fibrogenicity in idiopathic pulmonary fibrosis.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 273 Downloadable Samples
Affymetrix HT Human Genome U133A Array (hthgu133a), Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Systems biology of vaccination for seasonal influenza in humans.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 84 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Systems vaccinology has emerged as an interdisciplinary field that combines systems wide measurements and network and predictive modeling applied to vaccinology.
Publication Title
Systems biology of vaccination for seasonal influenza in humans.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 83 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Systems vaccinology has emerged as an interdisciplinary field that combines systems wide measurements and network and predictive modeling applied to vaccinology.
Publication Title
Systems biology of vaccination for seasonal influenza in humans.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 79 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Systems vaccinology has emerged as an interdisciplinary field that combines systems wide measurements and network and predictive modeling applied to vaccinology.
Publication Title
Systems biology of vaccination for seasonal influenza in humans.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 27 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Systems vaccinology has emerged as an interdisciplinary field that combines systems wide measurements and network and predictive modeling applied to vaccinology.
Publication Title
Systems biology of vaccination for seasonal influenza in humans.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Study of HP1 Knock Down on gene expression and splicing regulation in Human HeLa cells
Publication Title
Histone H3 lysine 9 trimethylation and HP1γ favor inclusion of alternative exons.
Sample Metadata Fields
Cell line
View Samples- Danio rerio
- 72 Downloadable Samples
- IlluminaHiSeq2000
Description
Both embryonic and adult zebrafish Mycobacterium marinum infection studies have contributed to our knowledge of the development and function of tuberculous granulomas, which are typical for mycobacterial pathogenesis. In this review we discuss how transcriptome profiling studies have helped to characterize this infection process and we include new RNA sequencing (RNA-Seq) data that reveals three main phases in the host response to M. marinum during the early stages of granuloma development in zebrafish embryos and larvae. The late-phase response shares common components with the strong and acute host transcriptome response that has previously been reported for S. typhimurium infection in zebrafish embryos. In contrast, the early/mid-phase response to M. marinum infection, characterized by suppressed pro-inflammatory signaling, is strikingly different from the acute response to S. typhimurium infection. Furthermore, M. marinum infection shows a collective and strongly fluctuating regulation of lipoproteins, while S. typhimurium infection has pronounced effects on amino acid metabolism and glycolysis. Overall design: Embryos were infected at 28 hpf by injecting 250 colony forming units of M. marinum Mma20 in 2%PVP into the caudal vein, or mock-injected with PBS/2%PVP. After injections, embryos were transferred into fresh egg water containing 0.003% 1-phenyl-2-thiourea (Sigma-Aldrich) to prevent melanization and incubated at 28°C. After the incubation period, infected and uninfected groups of 30 embryos were snap-frozen in liquid nitrogen and RNA was isolated for Illumina RNAseq analysis. Samples were taken at the following timepoints: 2, 4, 6, 8 hpi and 1, 2, 3, 4, 5 dpi.
Publication Title
Transcriptomic Approaches in the Zebrafish Model for Tuberculosis-Insights Into Host- and Pathogen-specific Determinants of the Innate Immune Response.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Human peroxisome biogenesis disorders are lethal genetic disease in which abnormal peroxisome assembly compromises overall peroxisome and cellular function. Peroxisomes are ubiquitous membrane-bound organelles involved in several important biochemical processes, notably lipid metabolism and the use of reactive oxygen species for detoxification. Using cultured cells, we systematically characterized the peroxisome assembly phenotypes associated with dsRNA-mediated knockdown of 14 predicted Drosophila homologs of PEX genes (encoding peroxins; required for peroxisome assembly and linked to peroxisome biogenesis disorders), and confirmed that at least 13 of them are required for normal peroxisome assembly. We also demonstrate the relevance of Drosophila as a genetic model for the early developmental defects associated with the human peroxisome biogenesis disorders. Mutation of the PEX1 gene is the most common cause of peroxisome biogenesis disorders and is one of the causes of the most severe form of the disease, Zellweger syndrome. Inherited mutations in Drosophila Pex1 correlate with reproducible defects during early development. Notably, Pex1 mutant larvae exhibit abnormalities that are analogous to those exhibited by Zellweger syndrome patients, including developmental delay, poor feeding, severe structural abnormalities in the peripheral and central nervous systems, and early death. Finally, microarray analysis defined clusters of genes whose expression varied significantly between wild-type and mutant larvae, implicating peroxisomal function in neuronal development, innate immunity, lipid and protein metabolism, gamete formation, and meiosis.
Publication Title
A Drosophila model for the Zellweger spectrum of peroxisome biogenesis disorders.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 30 Downloadable Samples
- Illumina Genome Analyzer II
Description
The roles of RNA-binding proteins as chaperones in the lifecycles of mRNAs are not well understood. The mammalian mitochondrial genome has been compressed over evolution to a size of just 16 kb, nevertheless the expression of its genes requires transcription, RNA processing, translation and RNA decay, much like the more complex chromosomal systems, providing an opportunity to use it as a model system to understand the fundamental aspects of gene expression. Here we combine RNase footprinting with PAR-CLIP at unprecedented depth to reveal the importance of RNA-protein interactions guided by the LRPPRC/SLIRP complex in dictating RNA folding within the mitochondrial transcriptome. We show that LRPPRC, in complex with its protein partner SLIRP, binds throughout the mitochondrial transcriptome, with a preference for mRNAs, and its loss affects the entire secondary structure and stability of the transcriptome. We demonstrate that the LRPPRC/SLIRP complex is a global RNA chaperone that stabilizes RNA structures to expose the required sites for translation, stabilization and polyadenylation. Our findings reveal a general mechanism where extensive RNA-protein interactions ensure that RNA is accessible for its biological functions. Overall design: RNase footprinting of LRPPRC and SLIRP knockout and control mice, in technical duplicate.
Publication Title
LRPPRC-mediated folding of the mitochondrial transcriptome.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples