Expansions of a hexanucleotide repeat (GGGGCC) in the noncoding region of the C9orf72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Decreased expression of C9orf72 is seen in expansion carriers, suggesting loss of function may play a role in disease. We find that two independent mouse lines lacking the C9orf72 ortholog (3110043O21Rik) in all tissues developed normally and aged without motor neuron disease. Instead, C9orf72 null mice developed progressive splenomegaly and lymphadenopathy with accumulation of engorged macrophage-like cells. C9orf72 expression was highest in myeloid cells, and loss of C9orf72 led to lysosomal accumulation and altered immune responses in macrophages and microglia, with age-related neuroinflammation similar to C9orf72 ALS but not sporadic ALS patient tissue. Thus, C9orf72 is required for normal function of myeloid cells, and altered microglial function may contribute to neurodegeneration in C9orf72 expansion carriers. Overall design: To compare the RNA Seq profiles from the lumbar region of spinal cords from mice lacking one copy or both copies of the C9orf72 ortholog (3110043O21Rik) compared to wild type control with two copies at 3 months (n=3) and 17 months (n=4).
C9orf72 is required for proper macrophage and microglial function in mice.
Specimen part, Cell line, Subject
View SamplesNoncoding expansions of a hexanucleotide repeat (GGGGCC) in the C9orf72 gene are the most common cause of familial amyotrophic lateral sclerosis and frontotemporal dementia. Here we report transgenic mice carrying a bacterial artificial chromosome (BAC) containing the full human C9orf72 gene with either a normal allele (15 repeats) or disease-associated expansion (~100–1,000 repeats; C9-BACexp). C9-BACexp mice displayed pathologic features seen in C9orf72 expansion patients, including widespread RNA foci and repeat-associated non-ATG (RAN) translated dipeptides, which were suppressed by antisense oligonucleotides targeting human C9orf72. Nucleolin distribution was altered, supporting that either C9orf72 transcripts or RAN dipeptides promote nucleolar dysfunction. Despite early and widespread production of RNA foci and RAN dipeptides in C9-BACexp mice, behavioral abnormalities and neurodegeneration were not observed even at advanced ages, supporting the hypothesis that RNA foci and RAN dipeptides occur presymptomatically and are not sufficient to drive neurodegeneration in mice at levels seen in patients. Overall design: To compare the RNA Seq profiles from the cortex and spinal cord of transgenic mice expressing unexpanded human C9orf72 (F08, n=4), expanded human C9orf72 (F112, n=3/4), and nontransgenic controls (n=4).
C9orf72 BAC Transgenic Mice Display Typical Pathologic Features of ALS/FTD.
Specimen part, Cell line, Subject
View SamplesGoal was to identify yeast genes whose expression changed as a function of the shift from growth in bulk culture to growth in an air-liquid interfacial biofilm.
Ethanol-independent biofilm formation by a flor wine yeast strain of Saccharomyces cerevisiae.
Specimen part
View SamplesComparison of gene expression profiles from C. elegans wildtype strain (N2) treated with L4440 and T25B9.1 RNAi for 5 days after L4 larvae stage. Jena Centre for Systems Biology of Ageing - JenAge (ww.jenage.de) Overall design: 6 samples in 2 groups: N2, L4440 5 days (3 Samples); N2, T25B9.1 5 days (3 Samples)
Impairing L-Threonine Catabolism Promotes Healthspan through Methylglyoxal-Mediated Proteohormesis.
Sex, Age, Specimen part, Cell line, Subject
View SamplesInfiltrating monocyte derived macrophages (MDMs) and resident microglia dominate CNS injury sites. We show that MDMs and microglia can directly communicate to modulate each others function. Also, the presence of MDMs in CNS injury suppresses microglia-mediated phagocytosis and inflammation. We suggest that macrophages infiltrating the injured CNS provide a mechanism to control acute and chronic microglia-mediated inflammation, which could otherwise drive damage in a variety of CNS conditions.
Peripherally derived macrophages modulate microglial function to reduce inflammation after CNS injury.
Sex, Specimen part, Treatment
View SamplesBackground: Arsenite is one of the most toxic chemical substances known and is assumed to exert detrimental effects on viability even at lowest concentrations. By contrast and unlike higher concentrations, we here find that exposure to low-dose arsenite promotes growth of cultured mammalian cells. In the nematode C. elegans, low-dose arsenite promotes resistance against thermal and chemical stressors, and extends lifespan of this metazoan, whereas higher concentrations reduce longevity. While arsenite causes a transient increase in reactive oxygen species (ROS) levels in C. elegans, co-exposure to ROS scavengers prevents the lifespan-extending capabilities of arsenite, indicating that transiently increased ROS levels act as transducers of arsenite effects on lifespan, a process known as mitohormesis. The RNA-seq data comprises 2 biological replicates for worms exposed to 100nM Arsenite 48h after L4 and 2 biological replicates of the same age as controls Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de) Overall design: 4 samples: 2 mRNA profiles of C.elegans 48h after L4 exposed to Arsenite; 2 mRNA profiles of C.elegans 48h after L4 as controls (H20). The N2 wild type (var. Bristol) strain was used.
Mitochondrial hormesis links low-dose arsenite exposure to lifespan extension.
Specimen part, Treatment, Subject
View SamplesThe Caenorhabditis elegans somatic gonad was the first organ to have its cell lineage determined, and the gonadal lineages of the two sexes differ greatly in their pattern of cell divisions, cell migration and cell types. Despite much study, the genetic pathways that direct early gonadal development and establish its sexual dimorphism remain largely unknown, with just a handful of regulatory genes identified from genetic screens. To help define the genetic networks that regulate gonadal development, we employed cell-specific RNA-seq. We identified transcripts present in Z1/Z4 or Z1/Z4 daughter cells in each sex at the onset of somatic gonadal sexual differentiation. For comparison, transcripts were identified in whole animals at both time points. Pairwise comparisons of samples identified several hundred gonad-enriched transcripts, including most known Z1/Z4-enriched mRNAs, and reporter analysis confirmed the effectiveness of this approach. Prior to the Z1/Z4 division few sex-biased Z1/Z4 transcripts were detectable, but less than six hours later, we identified more than 250 sex-biased transcripts in the Z1/Z4 daughters, of which about a third were enriched in the somatic gonad cells compared to cells from whole animals. This indicates that a robust sex-biased developmental program, some of it gonad-specific, initiates in these cells around the time of the first Z1/Z4 division. Cell-specific analysis also identified approximately 70 previously unannotated mRNA isoforms that are enriched in Z1/Z4 or their daughters. Our data suggest that early sex differentiation in the gonad is controlled by a relatively small suite of differentially expressed genes, even after dimorphism has become apparent. Overall design: 20 total sample: two time points, two sexes, and gonadal cells or whole animals. The earlier time point was collected in triplicate and was harvested 9.5 hours after starved, hatched L1s were fed. The later time point was collected in duplicate and was harvested 15 hour after starved, hatched L1 were fed. Replicates of either dissociated whole animals or gonadal cells (Z1/Z4 or Z1/Z4 daughter) from both male and hermaphrodites were harvested for each time point.
Cell-Specific mRNA Profiling of the Caenorhabditis elegans Somatic Gonadal Precursor Cells Identifies Suites of Sex-Biased and Gonad-Enriched Transcripts.
Sex, Specimen part, Subject, Time
View SamplesInnate and adaptive immune cells modulate heart failure pathogenesis during viral myocarditis, yet their identity and functions remain poorly defined. In this study we characterized the phenotype, life-cycle and function of different conventional dendritic cells (cDC) populations in the heart, with focus on the 2 major subsets (CD103+ and CD11b+), which differentially rely on local proliferation and precursor recruitment to maintain tissue residency. Following viral infection of the myocardium, cDCs accumulate in the heart coincident with monocyte infiltration and loss of resident reparative embryonic-derived cardiac macrophages. cDC depletion abrogates antigen-specific CD8+ T cell proliferative expansion, transforming subclinical cardiac injury to overt heart failure. Importantly, these effects are mediated by BATF3-dependent CD103+ cDCs. Collectively, our findings definitively identify resident cardiac cDC subsets, define their origins, and implicate an essential role for CD103+ cDCs in antigen-specific T cell responses during viral myocarditis.
A CD103<sup>+</sup> Conventional Dendritic Cell Surveillance System Prevents Development of Overt Heart Failure during Subclinical Viral Myocarditis.
Sex, Specimen part
View SamplesEven after decades of living in the same laboratory environment two Drosophila melanogaster strains originating from North America (Canton-S) and Central Russia (D18) demonstrate a few differentially expressed genes some of which may be important for local adaptation (e.g. genes responsible for insecticide resistance). Genes with different level of expression between Canton-S and D18 strains belong to important metabolic pathways, for instance energy metabolism, carbohydrate metabolic process, locomotion, body temperature rhythm regulation and tracheal network architecture.
Transcriptome analysis of <i>Drosophila melanogaster</i> laboratory strains of different geographical origin after long-term laboratory maintenance.
No sample metadata fields
View SamplesSteer liver transcriptome
Differential expression of genes related to gain and intake in the liver of beef cattle.
Sex, Specimen part
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