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SRP161805
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
- 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- 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- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Differences in the inherent properties of undifferentiated fat cell progenitors may contribute to the biological specificity of the abdominal subcutaneous (Sc) and visceral omental (V) fat depots. In this study, the biological characteristics of three distinct subpopulations of adipose tissue-derived stem cells (ASC), i.e. ASCSVF, ASCBottom and ASCCeiling isolated from Sc and V adipose tissue biopsies of non-obese subjects, were investigated. Genome-wide differential gene expression analysis followed by quantitative RT-PCR and analysis of cytokines in the ASC-derived conditioned medium were performed. By analysis of 28,869 annotated genes, 1,019 genes resulted differentially expressed between Sc-ASC and V-ASC. Within the Sc-ASC and V-ASC populations, 546 and 1,222, respectively, were the genes differentially expressed among ASCSVF, ASCBottom and ASCCeiling. A far more striking difference was found when the hierarchical clusters analysis was performed comparing each Sc-ASC with its own homologous V-ASC subset. mRNA levels of HoxA5, Tbx15, PI16, PITPNC1, FABP5, IL-6, IL-8, MCP-1, VEGF, MMP3, TFPI2, and ANXA10 were significantly different between Sc-ASC and V-ASC. Of the 27 cytokines measured, 14 (IL-2, IL-4, IL-5 IL-7, IL-9, IL-10, IL12, IL13, MIP1-, MIP1-, PDGF-, FGFbasic, GM-CSF, IP-10) were not released, whereas 13 were expressed (IL-1beta, IL-1ra, IL-15, IL-17, G-CSF, IFN, RANTES, TNF-, Eotaxin, IL-8, MCP-1, VEGF, IL-6), and of these, MCP-1, Eotaxin, IL-1ra, FGFbasic, IL-6, IL-8, G-CSF, and VEGF were significantly different among ASCSVF, ASCCeiling and ASCBottom of the two adipose tissue depots. These results demonstrate the existence of genetically and functionally heterogeneous fat-derived ASC populations, which may add to the complexity and specificity of Sc and V adipose tissue in humans.
Publication Title
Differences in gene expression and cytokine release profiles highlight the heterogeneity of distinct subsets of adipose tissue-derived stem cells in the subcutaneous and visceral adipose tissue in humans.
Sample Metadata Fields
Specimen part
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- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Mouse Embryonic Stem Cells (ESCs) express PDGFRa heterogeneously, fluctuating between a PDGFRa+ (PrE-primed) and a Platelet Endothelial Cell Adhesion Molecule 1 (PECAM1)-positive state (epiblast-primed). The two surface markers can be co-detected on a third subpopulation, expressing epiblast and PrE determinants. Overall design: Three different subpopulatiosn were sorted based on PECAM1/PDGFRa expression and analyzed by NGS
Publication Title
PDGFRα<sup>+</sup> Cells in Embryonic Stem Cell Cultures Represent the In Vitro Equivalent of the Pre-implantation Primitive Endoderm Precursors.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Ion Torrent Proton
Description
Objective: Alcoholic hepatitis (AH) is characterized by the expansion of ductular reaction (DR) cells and expression of liver progenitor cell (LPC) markers. The aim of this study was to identify the gene expression profile and associated genes of DR cells and to evaluate its weight in alcoholic disease progression. Design: KRT7+, KRT7- and total liver fractions were laser microdissected from liver biopsies (n=6) of patients with AH and whole transcriptome was sequenced. Gene signature was assessed in transcriptomic data from 41 patients with alcoholic liver disease. Pro-inflammatory profile was evaluated in tissue and serum samples and in human LPC organoids. Results: Transcriptome analysis of KRT7+ DR cells uncovered intrinsic gene pathways of DR and allowed identifying genes associated with DR expressed in AH. In addition, DR gene signature and associated genes correlated with disease progression and poor outcome in AH patients. Importantly, DR presented a pro-inflammatory profile with expression of CXC and CCL chemokines and was associated with infiltrating neutrophils. Moreover, LPC markers correlated with liver expression and circulating levels of inflammatory mediators. In vitro, human LPC organoids mimicked ductular reaction gene expression profile and produced chemokines. Moreover, LPC promoted neutrophil migration and enhanced their inflammatory profile. Conclusions: Here we report for the first time the gene expression signature of DR in AH and its association with disease progression. Functional and experimental analysis demonstrates that DR cells have a pro-inflammatory profile, and suggest their involvement in neutrophil recruitment and liver inflammatory response.
Publication Title
Ductular Reaction Cells Display an Inflammatory Profile and Recruit Neutrophils in Alcoholic Hepatitis.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Cell line, Treatment, Race
View Samples