Whole blood and spleen tissue was collected 15 (d15) or 44 (d44) days postimmunization from mice immunized with type II collagen on day 0 and immunostimulated on day 21.
Reactive Oxygen Species Regulate Both Priming and Established Arthritis, but with Different Mechanisms.
Sex, Specimen part
View SamplesDendritic cells (DCs) and macrophages (MPs) are important for immunological homeostasis in the colon. We found that F4/80hi CX3CR1hi (CD11b+CD103-) cells account for 80% of mouse colonic lamina propria (cLP) MHC-IIhi cells. Both CD11c+ and CD11c- cells within this population were identified as MPs based on multiple criteria, including a MP transcriptome revealed by microarray analysis. These MPs constitutively released high levels of IL-10 at least partially in response to the microbiota via an MyD88-independent mechanism. In contrast, cells expressing low to intermediate levels of F4/80 and CX3CR1 were identified as DCs, based on phenotypic and functional analysis and comprise three separate CD11chi cell populations: CD103+CX3CR1-CD11b- DCs, CD103+CX3CR1-CD11b+ DCs and CD103-CX3CR1intCD11b+ DCs. In non-inflammatory conditions, Ly6Chi monocytes differentiated primarily into CD11c+, but not CD11c- MPs. In contrast, during colitis, Ly6Chi monocytes massively invaded the colon and differentiated into pro-inflammatory CD103-CX3CR1intCD11b+ DCs, which produced high levels of IL-12, IL-23, iNOS and TNF. These findings demonstrate the dual capacity of Ly6Chi blood monocytes to differentiate into either regulatory MPs or inflammatory DCs in the colon, and that the balance of these immunologically antagonistic cell types is dictated by microenvironmental conditions.
Inflammation switches the differentiation program of Ly6Chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon.
No sample metadata fields
View SamplesCell lines derived from NK cell neoplasms were characterized using RNA sequencing and high-throughput drug sensitivity profiling to identify therapeutically actionable drivers in malignant NK cells. Overall design: RNA sequencing data was obtained from natural killer and T cell lines for gene expression profiling and mutation detection in parallel with drug sensitivity profiling. The ''NK_cell_line_GEO_drug_sensitivity.txt'' contains drug sensitivity scores of cell lines screened using 459 compounds. Breifly, compounds were preprinted on 384-well plates (Corning) in five different concentrations covering a 10,000-fold concentration range with an acoustic liquid handling device (Echo 550, Labcyte Inc.) and dissolved in 5 l culture medium on a shaker for 10 min. 20 l of single-cell suspension of cell lines (3,000 cells per well) were dispensed using Multi-Drop Combi peristaltic dispenser (Thermo Scientific). Plates were incubated at 37 C and 5% CO2 for 72 h after which cell viability was measured using CellTiter-Glo 2.0 reagent (Promega) according to the manufacturer s instructions with a Pherastar FS plate reader (BMG Labtech). Cell viability luminescence data were normalized to DMSO-only wells (negative control) and 100 mM benzethonium chloride-containing wells (positive control). The data were quantified using the drug sensitivity score (DSS) (Yadav et al., Scientific Reports 2014).
Aggressive natural killer-cell leukemia mutational landscape and drug profiling highlight JAK-STAT signaling as therapeutic target.
Specimen part, Cell line, Subject
View SamplesOur understanding of cellular mechanisms by which animals regulate their response to starvation is limited despite the close relevance of the problem to major human health issues. L1 diapause of Caenorhabditis elegans, where newly hatched first stage larval arrested in response to food-less environment, is an excellent system to study the problem. We found through genetic manipulation and lipid analysis that ceramide biosynthesis, particularly those with longer fatty acid side chains, critically impacts animal survival during L1 diapause. Genetic and expression analyses indicate that ceramide likely regulate this response by affecting gene expression and activity in multiple regulatory pathways known to regulate starvation-induced stress, including the insulin-IGF-1 signaling (IIS) pathway, Rb and other pathways that mediate pathogen/toxin/oxidative stress responses. These findings provide an important insight into the roles of sphingolipid metabolism in not only starvation response but also aging and food-response related human health problems.
Starvation-Induced Stress Response Is Critically Impacted by Ceramide Levels in Caenorhabditis elegans.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative DNA methylation and gene expression analyses identify DNA packaging and epigenetic regulatory genes associated with low motility sperm.
No sample metadata fields
View SamplesThe first embryonic cell divisions rely on maternally stored mRNA and proteins. The zygotic genome is initially transcriptionally silenced and activated later in a process called zygotic genome activation (ZGA). ZGA in any species is still a poorly understood process; the timing of transcription onset is controversial and the identity of the first transcribed genes unclear. Zebrafish, Danio rerio, is a rapidly developing vertebrate model, which is accessible to experimentation and global studies before, during and after ZGA. Overall design: To accurately determine the onset of ZGA and to identify the first transcripts in zebrafish, we developed a metabolic labeling method, utilizing the ribonucleotide analog 4-thio-UTP, which allows efficient and specific affinity purification of newly transcribed RNA. Using deep sequencing, we characterized the onset of transcription in zebrafish embryos at 128-, 256-, and 512-cell stages. We identified 592 nuclear-encoded zygotically transcribed genes, comprising 670 transcript isoforms. Mitochondrial genomes were highly transcribed at all time points. Further, bioinformatic analysis revealed an enrichment of transcription factors and miRNAs among the newly transcribed genes, suggesting mechanistic roles for the early genes that are required to activate subsequent gene expression programs in development. Interestingly, analysis of gene-architecture revealed that zygotically transcribed genes are often intronless and short, reducing transcription and processing time of the transcript. The newly generated dataset enabled us to compare zygotically transcribed genes over a broad phylogenetic distance with fly and mouse early zygotic genes. This analysis revealed that short gene length is a common characteristic for early zygotically expressed genes. However, we detected a poor level of overlap for shared orthologs.
The earliest transcribed zygotic genes are short, newly evolved, and different across species.
No sample metadata fields
View SamplesAcute myeloid leukemia (AML) is characterized by molecular heterogeneity. As commonly altered genomic regions point to candidate genes involved in leukemogenesis, we used microarray-based comparative genomic hybridization and single nucleotide polymorphism profiling data of 391 AML cases to further narrow down genomic regions of interest. Targeted-resequencing of 1000 genes located in the critical regions was performed in a representative cohort of 50 AML samples comprising all major cytogenetic subgroups. We identified 120 missense/nonsense mutations as well as 60 insertions/deletions affecting 73 different genes (~3.6 tumor-specific aberrations/AML). While most of the newly identified alterations were non-recurrent, we observed a number of mutations affecting genes involved in epigenetic regulation including known candidates like TET2, TET1, DNMT3A and DNMT1, as well as mutations in the histone methyltransferases NSD1, EZH2 and MLL3. Furthermore, we found mutations in the splicing factor SFPQ and in the non-classical regulators of mRNA-processing CTCF and RAD21. These splicing-related mutations affected 10% of AML patients in a mutually exclusive manner. In conclusion, we could identify a significant enrichment of alterations in genes involved in aberrant splicing and epigenetic regulation in genomic regions commonly altered in AML, highlighting their important role in the molecular pathogenesis of AML.
Commonly altered genomic regions in acute myeloid leukemia are enriched for somatic mutations involved in chromatin remodeling and splicing.
Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptional profiles underlying parent-of-origin effects in seeds of Arabidopsis thaliana.
No sample metadata fields
View SamplesCrossing plants of the same species but different ploidies can have dramatic effects on seed growth, but little is known about the alterations to transcriptional programmes responsible for this. Parental genomic imbalance particularly affects proliferation of the endosperm, with an increased ratio of paternally to maternally contributed genomes (paternal excess) associated with overproliferation, while maternal excess inhibits endosperm growth. One interpretation is that interploidy crosses disrupt the balance in the seed of active copies of parentally imprinted genes. This is supported by the observation that mutations in imprinted FIS-class genes of Arabidopsis thaliana share many features of the paternal excess phenotype. Here we investigated gene expression underlying parent-of-origin effects in Arabidopsis through transcriptional profiling of siliques generated by interploidy crosses and FIS-class mutants.
Transcriptional profiles underlying parent-of-origin effects in seeds of Arabidopsis thaliana.
No sample metadata fields
View SamplesThe following abstract from the submitted manuscript describes the major findings of this work.
A role for peroxisome proliferator-activated receptor γ coactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth.
Specimen part
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