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SRP101878
Mus musculus
18 Downloadable Samples
NextSeq 500
Description
Monocytes are derived from hematopoietic stem cells through a series of intermediate progenitor stages, but the factors that regulate this process are incompletely defined. Using a Ccr2/Cx3cr1 dual-reporter system to model murine monocyte ontogeny, we conducted a small molecule screen that identified an essential role of mechanistic target of rapamycin complex 1 (mTORC1) in the development of monocytes and other myeloid cells. Overall design: Examination of gene expression in 1) Granulocyte-Monocyte Progenitors from Raptor KO mice, Tsc2 KO mice and controls; and 2) DR-ER-Hoxb8 cells differentiated in the presence of DMSO, rapamycin or SL0101-01
Publication Title
The metabolic regulator mTORC1 controls terminal myeloid differentiation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 50 Downloadable Samples
- Illumina HiSeq 2500
Description
The mechanisms that determine the efficacy or inefficacy of methotrexate in juvenile idiopathic arthritis (JIA) are ill-defined. The objective of this study was to identify a gene expression transcriptional signature associated with poor response to MTX in patients with JIA. RNA sequencing was used to measure gene expression in peripheral blood mononuclear cells (PBMC) collected from 47 patients with JIA prior to MTX treatment and 14 age-matched controls. Biological differences between all JIA patients and controls were explored by constructing a signature of differentially expressed genes. Unsupervised clustering and pathway analysis was performed. Transcriptional profiles were compared to a reference gene expression database representing sorted cell populations, including B and T lymphocytes, and monocytes. A signature of 99 differentially expressed genes (Bonferroni-corrected p<0.05) capturing the biological differences between all JIA patients and controls was identified. Unsupervised clustering of samples based on this list of 99 genes produced subgroups enriched for MTX response status. Comparing this gene signature to reference signatures from sorted cell populations revealed high concordance between the expression profiles of monocytes and of MTX non-responders. CXCL8 (IL-8) was the most significantly differentially expressed gene transcript comparing all JIA patients to controls (Bonferroni-corrected p=4.12E-10). Variability in clinical response to methotrexate in JIA patients is associated with differences in gene transcripts modulated in monocytes. These gene expression profiles may provide a basis for biomarkers predictive of treatment response. Overall design: Peripheral blood mononuclear cells (PBMC) collected from 47 patients with JIA prior to MTX treatment and 14 age-matched controls
Publication Title
Transcriptional profiles of JIA patient blood with subsequent poor response to methotrexate.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 36 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Transcriptomics of distinct subpopulations of synovial fibroblasts from osteoarthritis and rheumatoid arthritis arthroplasty tissues.
Publication Title
Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis.
Sample Metadata Fields
Sex, Age, Disease
View Samples- Homo sapiens
- 298 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The use of microbiological cultures for diagnosing bacterial infections in young febrile infants have substantial limitations, including false positive and false negative cultures, and non-ideal turn-around times. Analysis of host genomic expression patterns (RNA biosignatures) in response to the presence of specific pathogens, however, may provide an alternate and potentially improved diagnostic approach. This study was designed to define bacterial and non-bacterial RNA biosignatures to distinguish these infections in young febrile infants.
Publication Title
Association of RNA Biosignatures With Bacterial Infections in Febrile Infants Aged 60 Days or Younger.
Sample Metadata Fields
Sex, Age, Specimen part, Race
View Samples- Mus musculus
- 23 Downloadable Samples
- Illumina HiSeq 2500
Description
Cortical interneurons display a remarkable diversity in their morphology, physiological properties and connectivity. Elucidating the molecular determinants underlying this heterogeneity is essential for understanding interneuron development and function. We discovered that alternative splicing differentially regulates the integration of somatostatin- and parvalbumin-expressing interneurons into nascent cortical circuits through the cell-type specific tailoring of mRNAs. Specifically, we identified a role for the activity-dependent splicing regulator Rbfox1 in the development of cortical interneuron subtype specific efferent connectivity. Our work demonstrates that Rbfox1 mediates largely non-overlapping alternative splicing programs within two distinct but related classes of interneurons. Overall design: RNA-seq of FACS sorted PV+ and SST+ cortical interneuronals at P8 of wt and conditional Rbfox1 Kos
Publication Title
Rbfox1 Mediates Cell-type-Specific Splicing in Cortical Interneurons.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Identifying the differentially expressed genes between ADI-PEG20 resistant and parental Ju77 cell line
Publication Title
Inhibition of the Polyamine Synthesis Pathway Is Synthetically Lethal with Loss of Argininosuccinate Synthase 1.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 200 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Novel prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis. One tumor class displaying neuronal lineage markers shows longer survival, while two tumor classes enriched for neural stem cell markers display equally short survival. Poor prognosis subclasses exhibit either markers of proliferation or of angiogenesis and mesenchyme. Analysis of gene expression data is described in Phillips et al., Cancer Cell, 2006.
Publication Title
Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis.
Sample Metadata Fields
Sex, Age, Disease stage
View Samples- Homo sapiens
- 81 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Acute lymphoblastic pediatric leukemia specimens without known genetic hallmarks are examined for hidden genomic aberrancies and related gene expression profiles
Publication Title
Integration of genomic and gene expression data of childhood ALL without known aberrations identifies subgroups with specific genetic hallmarks.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Compelling evidence suggests that mitochondrial dysfunction contributes to the pathogenesis of heart failure, including defects in the substrate oxidation, and the electron transport chain (ETC) and oxidative phosphorylation (OXPHOS). However, whether such changes occur early in the development of heart failure, and are potentially involved in the pathologic events that lead to cardiac dysfunction is unknown. To address this question, we conducted transcriptomic/metabolomics profiling in hearts of mice with two progressive stages of pressure overload-induced cardiac hypetrophy: i) cardiac hypertrophy with preserved ventricular function achieved via transverse aortic constriction for 4 weeks (TAC) and ii) decompensated cardiac hypertrophy or heart failure (HF) caused by combining 4 wk TAC with a small apical myocardial infarction. Transcriptomic analyses revealed, as shown previously, downregulated expression of genes involved in mitochondrial fatty acid oxidation in both TAC and HF hearts compared to sham-operated control hearts. Surprisingly, however, there were very few changes in expression of genes involved in other mitochondrial energy transduction pathways, ETC, or OXPHOS. Metabolomic analyses demonstrated significant alterations in pathway metabolite levels in HF (but not in TAC), including elevations in acylcarnitines, a subset of amino acids, and the lactate/pyruvate ratio. In contrast, the majority of organic acids were lower than controls. This metabolite profile suggests bottlenecks in the carbon substrate input to the TCA cycle. This transcriptomic/metabolomic profile was markedly different from that of mice PGC-1a/b deficiency in which a global downregulation of genes involved in mitochondrial ETC and OXPHOS was noted. In addition, the transcriptomic/metabolomic signatures of HF differed markedly from that of the exercise-trained mouse heart. We conclude that in contrast to current dogma, alterations in mitochondrial metabolism that occur early in the development of heart failure reflect largely post-transcriptional mechanisms resulting in impedance to substrate flux into the TCA cycle, reflected by alterations in the metabolome.
Publication Title
Energy metabolic reprogramming in the hypertrophied and early stage failing heart: a multisystems approach.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples