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SRP072106
Mus musculus
23 Downloadable Samples
Illumina HiSeq 2000, NextSeq 500
Description
Local mRNA translation mediates the adaptive responses of axons to extrinsic signals but direct evidence that it occurs in mammalian CNS axons in vivo is scant. We developed an axon-TRAP-RiboTag approach in mouse that allows deep-sequencing analysis of ribosome-bound mRNAs in the retinal ganglion cell axons of the developing and adult retinotectal projection in vivo. The embryonic-to-postnatal axonal translatome comprises an evolving subset of enriched genes with axon-specific roles suggesting distinct steps in axon wiring, such as elongation, pruning and synaptogenesis. Adult axons, remarkably, have a complex translatome with strong links to axon survival, neurotransmission and neurodegenerative disease. Translationally co-regulated mRNA subsets share common upstream regulators, and novel sequence elements generated by alternative splicing that promote axonal mRNA translation. Our results indicate that intricate regulation of compartment-specific mRNA translation in mammalian CNS axons supports the formation and maintenance of neural circuits in vivo. Overall design: The profiling of ribosome-bound mRNAs in mouse retinal ganglion cell axons at 4 different developmental stages
Publication Title
On-Site Ribosome Remodeling by Locally Synthesized Ribosomal Proteins in Axons.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Chronic viral infections are characterized by a state of CD8 T cell dysfunction termed exhaustion. A better understanding of the mechanisms that regulate CD8 T cell responses during chronic infection is required to improve immunotherapies that restore function in exhausted CD8 T cells. Here we identify a novel population of virus-specific CD8 T cells with a T follicular helper (Tfh)-like signature in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). These Tfh-like CD8 T cells expressed the programmed cell death-1 (PD-1) inhibitory receptor but at the same time also expressed co-stimulatory molecules and had a gene signature that was related to CD8 T cell memory precursor cells and hematopoietic stem cells (HSC). These Tfh-like CD8 T cells acted as stem cells during chronic infection undergoing self-renewal and also differentiating into the terminally exhausted CD8 T cells that were present in both lymphoid and non-lymphoid tissues. The Tfh-like CD8 T cells were found only in lymphoid tissues and resided predominantly in the T cell zones along with nave CD8 T cells. Interestingly, the proliferative burst after PD-1 blockade came almost exclusively from this Tfh-like CD8 T cell subset. Importantly, the transcription factor TCF1 played a cell intrinsic and essential role in the generation of Tfh-like CD8 T cells. Taken together, our study identifies Tfh-like CD8 T cells as the critical subset for maintaining the pool of virus-specific CD8 T cells during chronic infection and as the cells that proliferate after PD-1 blockade. These findings provide a better understanding of T cell exhaustion and have implications towards optimizing PD-1 directed immunotherapy.
Publication Title
Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Chronic cold exposure causes white adipose tissue (WAT) to adopt features of brown adipose tissue, a process known as browning. Previous studies have hinted at a possible role for the transcription factor Peroxisome Proliferator-Activated Receptor alpha (PPAR) in cold-induced browning. Here we aimed to investigate the importance of PPAR in driving transcriptional changes during cold-induced browning in mice. Male wildtype and PPAR/ mice were housed at thermoneutrality (28 C) or cold (5 C) for 10 days. Whole genome expression analysis was performed on inguinal WAT. In addition, other analyses were carried out. Whole genome expression data of livers of wildtype and PPAR/ mice fasted for 24 h served as positive control for PPAR-dependent gene regulation.Cold exposure increased food intake and decreased weight of BAT and WAT to a similar extent in wildtype and PPAR/ mice. Except for plasma non-esterified fatty acids, none of the cold-induced changes in plasma metabolites were dependent on PPAR genotype. Histological analysis of inguinal WAT showed clear browning upon cold exposure but did not reveal any morphological differences between wildtype and PPAR/ mice. Transcriptomics analysis of inguinal WAT showed a marked effect of cold on overall gene expression, as revealed by principle component analysis and hierarchical clustering. However, wildtype and PPAR/ mice clustered together, even after cold exposure, indicating a similar overall gene expression profile in the two genotypes. Pathway analysis revealed that cold upregulated pathways involved in energy usage, oxidative phosphorylation, and fatty acid -oxidation to a similar extent in wildtype and PPAR/ mice. Furthermore, cold-mediated induction of genes related to thermogenesis such as Ucp1, Elovl3, Cox7a1, Cox8, and Cidea, as well as many PPAR target genes, was similar in wildtype and PPAR/ mice. Finally, pharmacological PPAR activation had a minimal effect on expression of cold-induced genes in murine WAT.Cold-induced changes in gene expression in inguinal WAT are unaltered in mice lacking PPAR, indicating that PPAR is dispensable for cold-induced browning.
Publication Title
The Peroxisome Proliferator-Activated Receptor α is dispensable for cold-induced adipose tissue browning in mice.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
Culturing myotubes from skeletal muscle (SM) biopsies enables investigating transcriptional defects and assaying therapeutic strategies. This study compares the transcriptome of aneurally cultured human SM cells versus that of tissue biopsies.
Publication Title
Comparative gene expression profiling between human cultured myotubes and skeletal muscle tissue.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- NextSeq 500
Description
We identified a subset of hepatocytes with high Telomerase Reverse transcriptase (Tert) that functions as the repopulating stem cells in homeostasis and injury. We performed RNA-Seq to reveal the differences of these cells and the other hepatocytes. Overall design: RNA mRNA profiles of TERT(High) and TERT (Low) hepatocytes from 2-month old mice were generated by deep sequencing, in triplicate, using Illumina platform.
Publication Title
Distributed hepatocytes expressing telomerase repopulate the liver in homeostasis and injury.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Status Epilepticus (SE) is an abnormally prolonged seizure that results from either a failure of mechanisms that terminate seizures or from initiating mechanisms that inherently lead to prolonged seizures.
Publication Title
Induction of Type 2 Iodothyronine Deiodinase After Status Epilepticus Modifies Hippocampal Gene Expression in Male Mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: We report the detailed development of biomarkers to predict the clinical outcome under dengue infection. Transcriptional signatures from purified peripheral blood mononuclear cells were derived from whole-genome gene-expression microarray data and validated by quantitative PCR and tested in independent samples. Methodology/Principal Findings: The study was performed on patients of a well-characterized dengue cohort from Recife, Brazil. The samples analyzed were collected prospectively from acute febrile dengue patients who evolved with different degrees of disease severity, classic dengue fever or dengue hemorrhagic fever (DHF) and compared with similar samples from other non-dengue febrile illnesses. The DHF samples were collected 2-3 days before the presentation of the plasma leakage symptoms. Differentially-expressed genes were selected by univariate statistical tests as well as multivariate classification techniques. The results showed that at early stages of dengue infection, the genes involved in effector mechanisms of innate immune response presented a weaker activation on patients who later developed hemorrhagic fever, whereas the genes involved in apoptosis were expressed in higher levels. Conclusions/Significance: Some of the gene expression signatures displayed estimated accuracy rates of more than 95%, indicating that expression profiling with these signatures may provide a useful means of DHF prognosis at early stages of infection
Publication Title
Gene expression profiling during early acute febrile stage of dengue infection can predict the disease outcome.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
In order to gain insight into the molecular pathogenesis of collagen VI defects we have performed gene expression microarray analysis of dermal fibroblasts. We have compared the transcriptome of fibroblasts, treated or untreated with ascorbic acid, from UCMD patients (n = 6) and aged-matched healthy children (n = 5).
Publication Title
Transcriptome Analysis of Ullrich Congenital Muscular Dystrophy Fibroblasts Reveals a Disease Extracellular Matrix Signature and Key Molecular Regulators.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 50 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Comparative transcriptome analysis of human skeletal muscle in response to cold acclimation and exercise training in human volunteers.
Sample Metadata Fields
Sex, Disease, Subject, Time
View Samples- Homo sapiens
- 36 Downloadable Samples
Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Background: Cold acclimation and exercise training were previously shown to increase peripheral insulin sensitivity in human volunteers with type 2 diabetes. Although cold is a potent activator of brown adipose tissue, the increase in peripheral insulin sensitivity by cold is largely mediated by events occurring in skeletal muscle and at least partly involves GLUT4 translocation, as is also observed for exercise training. Results: To investigate if cold acclimation and exercise training overlap in the molecular adaptive response in skeletal muscle, we performed transcriptomics analysis on vastus lateralis muscle collected from human subjects before and after 10 days of cold acclimation, as well as before and after a 12-week exercise training intervention. Methods: Cold acclimation altered the expression of 756 genes (422 up, 334 down, P<0.01), while exercise training altered the expression of 665 genes (444 up, 221 down, P<0.01). Principal Component Analysis, Venn diagram, similarity analysis and Rank–rank Hypergeometric Overlap all indicated significant overlap between cold acclimation and exercise training in upregulated genes, but not in downregulated genes. Overlapping gene regulation was especially evident for genes and pathways associated with extracellular matrix remodeling. Interestingly, the genes most highly induced by cold acclimation were involved in contraction and in signal transduction between nerve and muscle cells, while no significant changes were observed in genes and pathways related to insulin signaling or glucose metabolism. Conclusions: Overall, our results indicate that cold acclimation and exercise training have overlapping effects on gene expression in human skeletal muscle, but strikingly these overlapping genes are designated to pathways related to cell remodeling rather than metabolic pathways.
Publication Title
Comparative transcriptome analysis of human skeletal muscle in response to cold acclimation and exercise training in human volunteers.
Sample Metadata Fields
Sex, Disease, Subject, Time
View Samples