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Mus musculus
12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The activity of chaperone-mediated autophagy (CMA), a catabolic pathway for selective degradation of cytosolic proteins in lysosomes, decreases with age, but the consequences of this functional decline in vivo remain unknown. In this work, we have generated a conditional knockout mouse to selectively block CMA in liver. We have found that blockage of CMA causes hepatic glycogen depletion and hepatosteatosis. The liver phenotype is accompanied by reduced peripheral adiposity, increased energy expenditure, and altered glucose homeostasis. Comparative lysosomal proteomics revealed that key enzymes in carbohydrate and lipid metabolism are normally degraded by CMA and that impairment of this regulated degradation contributes to the metabolic abnormalities observed in CMA-defective animals. These findings highlight the involvement of CMA in regulating hepatic metabolism and suggest that the age-related decline in CMA may have a negative impact on the energetic balance of old organisms.
Publication Title
Deficient chaperone-mediated autophagy in liver leads to metabolic dysregulation.
Sample Metadata Fields
Specimen part
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SRP078318- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
Embryonic retinal development Overall design: Mouse retinas at different embryonic developmental stages were isolated and mRNA expression was determined by RNA sequencing
Publication Title
Programmed mitophagy is essential for the glycolytic switch during cell differentiation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 101 Downloadable Samples
- Affymetrix Clariom S Pico Assay HT (clariomshumanht)
Description
Eight healthy human subjects were enrolled in a 6-day simulated shift work protocol. Blood samples were collected during the two 24-hour measurement periods. Blood samples were collected every 4 hours during both measurement periods. Subjects entered the lab on Day 1. At the start of Day 2, the first 24-hour measurement period was started. Subjects slept according to their habitual sleep/wake schedule, followed by a 16-hour constant posture procedure. On days 3-6, the sleep period was delayed by 10 hours. Following the third night on this schedule, subjects underwent another 24-hour measurement period. During both measurement periods, 7 blood samples were collected and PBMCs were isolated. mRNA was extracted, labelled, and hybridized to microarrays.
Publication Title
Simulated night shift work induces circadian misalignment of the human peripheral blood mononuclear cell transcriptome.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 33 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Old C57BL/6 mice cannot mount an effective innate immune response
Publication Title
Aged mice are unable to mount an effective myeloid response to sepsis.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We quantified differential gene (mRNA) expression in human coronary artery cells treated with native HDL, reconstituted HDL, lipid-free apolipoprotein A-I, small unilamellar vesicles, or PBS control.
Publication Title
HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 72 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Calorie restriction (CR) is the most robust non-genetic intervention to universally delay the onset of age-related diseases and extend mean and maximum lifespan. However, species, strain, sex, diet, age of onset, and level of CR are emerging as important variables to consider for a successful CR response. Here, we investigated the role of strain, sex and level of CR on outcomes of health and survival in mice. Response to CR varied from lifespan extension to no effect on survival, while consistently delaying the onset and impact of diseases independently of strain, sex and level of dietary restriction. CR led to transcriptional and metabolomics changes in the liver indicating anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. Additionally, CR prevented the age-associated decline in the proteostasis network. Further, CR increased mitochondrial number and preserved their ultrastructure and function with age. Abrogation of mitochondrial function by deletion of fumarate hydratase or malate dehydrogenase 2 negated the life-prolonging effects of CR in yeast and worms. In F1 hybrid strains of mice, the lifespan response to CR tracked with the dam, indicating that the mitochondrial haplotype is an important regulator of CR. Our data illustrate the complexity of the CR responses within a single animal species in the context of aging, with a clear separation of outcomes related to health and survival, highlighting the complexities of translation of CR into human interventions.
Publication Title
Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
CD4+ T helper lymphocytes that express interleukin-17 (Th17 cells) have critical roles in mouse models of autoimmunity, and there is mounting evidence that they also influence inflammatory processes in humans. Genome-wide association studies in humans have linked genes involved in Th17 cell differentiation and function with susceptibility to Crohns disease, rheumatoid arthritis, and psoriasis1-3. Thus, the pathway towards differentiation of Th17 cells and, perhaps, of related innate lymphoid cells with similar effector functions4, 5, is an attractive target for therapeutic applications. Mouse and human Th17 cells are distinguished by expression of the retinoic acid receptor-related orphan nuclear receptor RORt, which is required for induction of IL-17 transcription and for the manifestation of Th17-dependent autoimmune disease in mice6. By performing a chemical screen with an insect cell-based reporter system, we identified the cardiac glycoside digoxin as a specific inhibitor of RORt transcriptional activity. Digoxin inhibited murine Th17 cell differentiation without affecting differentiation of other T cell lineages and was effective in delaying the onset and reducing the severity of autoimmune disease in mice. At high concentrations, digoxin is toxic for human cells, but non-toxic synthetic derivatives, 20,22-dihydrodigoxin-21,23-diol (Dig(dhd)) and digoxin-21-salicylidene (Dig(sal)), specifically inhibited induction of IL-17 in human CD4+ T cells. Using these small molecule compounds, we demonstrated that RORt is imporant for the maintenance of IL-17 expression in mouse and human effector T cells. These data suggest that derivatives of digoxin can be used as chemical probes for development of RORt-targeted therapeutic agents that attenuate inflammatory lymphocyte function and autoimmune disease.
Publication Title
Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 35 Downloadable Samples
- Illumina HiSeq 4000
Description
The tumor suppressor protein 53BP1, a pivotal regulator of DNA double-strand break (DSB) repair, was first identified as a p53-interacting protein over two decades ago, however its direct contributions to p53-dependent cellular activities remain undefined. Here, we reveal 53BP1 stimulates genome-wide p53-dependent gene transactivation and repression events in response to ionizing radiation (IR) and synthetic p53 activation. 53BP1-dependent p53 modulation requires both auto-oligomerization and tandem-BRCT domain mediated bivalent interactions with p53 and the ubiquitin-specific protease USP28. Loss of these activities results in inefficient p53-dependent cell-cycle checkpoint and exit responses. Furthermore, we demonstrate 53BP1-USP28 cooperation to be essential for normal p53-promoter element interactions and gene transactivation-associated events, yet dispensable for 53BP1-dependent DSB repair regulation. Collectively, our data provides a mechanistic explanation for 53BP1-p53 cooperation in controlling anti-tumorigenic cell fate decisions, and reveal these activities to be distinct and separable from 53BP1’s regulation of DNA double-strand break repair pathway choice. Overall design: We evaluated the transcriptional profiles of two 53BP1? cell lines and included a positive (WT) and a negative (p53?) controls. These cell lines were treated with Nutlin-3, ionising radiation or mock treated. Three independent replicates were included for each independent condition generating a total of 36 samples.
Publication Title
53BP1 Integrates DNA Repair and p53-Dependent Cell Fate Decisions via Distinct Mechanisms.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Discoid lupus erythematosus (DLE) is the most common skin manifestation of lupus. Despite its high frequency in systemic lupus in addition to cases without extracutaneous manifestations, targeted treatments for DLE are lacking, likely because of a dearth of knowledge of the molecular landscape of DLE skin. Here, we profiled the transcriptome of DLE skin in order to identify signaling pathways and cellular signatures that may be targeted for treatment purposes. Further comparison of the DLE transcriptome with that of psoriasis, a useful reference given our extensive knowledge of molecular pathways in this disease, provided a framework to identify potential therapeutic targets. Although a growing body of data support a role for IL-17 and T helper type 17 (Th17) cells in systemic lupus, we show a relative enrichment of IFN--associated genes without that for IL-17-associated genes in DLE. Extraction of T cells from the skin of DLE patients identified a predominance of IFN--producing Th1 cells and an absence of IL-17-producing Th17 cells, complementing the results from whole-skin transcriptomic analyses. These data therefore support investigations into treatments for DLE that target Th1 cells or the IFN- signaling pathway.
Publication Title
Dominant Th1 and minimal Th17 skewing in discoid lupus revealed by transcriptomic comparison with psoriasis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Arabidopsis thaliana
- 9 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We analysed the transcriptome of dry seeds (the end product of seed maturation) of three genotypes with different DOG1 expression levels. These included the WT Ler (low DOG1 expression), the near isogenic line NILDOG1-Cvi (strong DOG1 expression) and the non-dormant dog1-1 mutant (absence of DOG1 expression). NILDOG1-Cvi is the Ler WT containing an introgression of the Cvi accession on chromosome 5, which includes the DOG1 gene (Bentsink et al., 2006). The dog1-1 mutant is in the NILDOG1-Cvi genetic background.
Publication Title
The Arabidopsis DELAY OF GERMINATION 1 gene affects ABSCISIC ACID INSENSITIVE 5 (ABI5) expression and genetically interacts with ABI3 during Arabidopsis seed development.
Sample Metadata Fields
Specimen part
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