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SRP090129
Mus musculus
9 Downloadable Samples
Illumina HiSeq 2000
Description
RNA-Sequencing (RNA-seq). The aim of this RNA-seq experiment was to monitor the genome-wide transcriptional changes in mouse embryonic stem cells depleted of either Fam60a or Sin3a. Overall design: RNA-Seq of mRNA level of mESCs depleted for Sin3a and Fam60a.
Publication Title
Fam60a defines a variant Sin3a-Hdac complex in embryonic stem cells required for self-renewal.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
To follow-up findings that miR-9 was abundantly expressed in control NPCs, significantly down-regulated in a subset of SZ NPCs, and that miR-9 levels/activity, neural migration and diagnosis were strongly correlated, we tested the effect of manipulating miR-9 at cellular, proteomic and transcriptomic levels. Unexpectedly, proteomic- and RNAseq-based analysis revealed that these effects were mediated primarily by small changes in expression of indirect miR-9 targets, rather than large changes in direct miR-9 targets; these indirect targets are enriched for migration-associated genes. Together these data indicate that aberrant levels and activity of miR-9 may be one of the many factors that contribute to SZ risk, at least in a subset of patients. Methods: We compared global transcription of forebrain NPCs from two control and two SZ patients with manipulated miR-9 levels by RNAseq. Results: Although RNAseq analysis revealed large inter-individual heterogeneity, we were able to resolve several functional consistencies in the effects of our miR-9 perturbations: i) the change in miR-9 activity was consistent with the inhibitory role of miR-9, ii) the gene expression fold-change of miR-9 target genes (between each perturbation and its corresponding control, summarized by the first principal component) was correlated (r=0.95, p=3.92e-04) with miR-9 fold change and iii) the differentially expressed (DE; p <0.01) gene list resulting from miR-9 perturbation (paired t-test) was enriched for miR-9 targets (1.53-fold, p=1.2e-5). Conclusions: We integrated the miR-9 perturbation RNAseq data with our existing RNAseq datasets contrasting control and SZ hiPSC NPC expression from our cohort 1 (six controls, four patients), to ask whether there was any relationship between the “SZ NPC signature” and “miR-9 perturbation” datasets; we observed that the DE (p-value <0.01) in “SZ NPC signature” is enriched for DE (fdr<0.01) in “miR-9 perturbation” (the overall enrichment is 2.31-fold (p=9.39e-09)); there is significant correlation between DE fold-change in these two datasets (overall genes r=0.188; p<10e-50). Effects were mediated primarily by small changes in expression of indirect miR-9 targets, rather than large changes in direct miR-9 targets; these indirect targets are enriched for migration-associated genes Overall design: Biological duplicates of passage-matched NPCs from 1 control (female) and 1 SZ patient (female) were transduced with either RV-GFP or RV-miR-9-GFP; GFP-positive NPCs were purified by fluorescent activated cell sorting (FACS) and expanded for two passages. In parallel, passage-matched NPCs from 2 controls (1 male, 1 female) and 2 SZ patients (1 male, 1 female) were transiently transfected with either scrambled or miR-9 LNA probes. In both instances, miR-9 perturbation was confirmed by qPCR.
Publication Title
Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells.
Sample Metadata Fields
Sex, Specimen part, Disease, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
Cell-based models of many neurological and psychiatric diseases, established by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), have now been reported. While numerous reports have demonstrated that neuronal cells differentiated from hiPSCs are electrophysiologically active mature neurons, the “age” of these cells relative to cells in the human brain remains unresolved. Comparisons of gene expression profiles of hiPSC-derived neural progenitor cells (NPCs) and neurons to the Allen BrainSpan Atlas indicate that hiPSC neural cells most resemble first trimester neural tissue. Consequently, we posit that hiPSC-derived neural cells may most accurately be used to model the early developmental defects that contribute to disease predisposition rather than the late features of the disease. Though the characteristic symptoms of schizophrenia SZ generally appear late in adolescence, it is now thought to be a neurodevelopmental condition, often predated by a prodromal period that can appear in early childhood. Postmortem studies of SZ brain tissue typically describe defects in mature neurons, such as reduced neuronal size and spine density in the prefrontal cortex and hippocampus, but abnormalities of neuronal organization, particularly in the cortex, have also been reported. We postulated that defects in cortical organization in SZ might result from abnormal migration of neural cells. To test this hypothesis, we directly reprogrammed fibroblasts from SZ patients into hiPSCs and subsequently differentiated these disorder-specific hiPSCs into NPCs. SZ hiPSC differentiated into forebrain NPCs have altered expression of a number of cellular adhesion genes and WNT signaling. Methods: We compared global transcription of forebrain NPCs from six control and four SZ patients by RNAseq. Results: Multi-dimensional scaling (MDS) resolved most SZ and control hiPSC NPC samples; 848 genes were significantly differentially expressed (FDR<0.01) Conclusions: The WNT signaling pathway was enriched 2-fold (fisher exact test p-value = 0.031). Overall design: 1-2 independent differentiations (biological replicates) for each of four control and four schizophrenia patients were analyzed; samples were generated in parallel to neuron RNAseq data.
Publication Title
Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
- Illumina HiSeq 2000, NextSeq 500
Description
Local mRNA translation mediates the adaptive responses of axons to extrinsic signals but direct evidence that it occurs in mammalian CNS axons in vivo is scant. We developed an axon-TRAP-RiboTag approach in mouse that allows deep-sequencing analysis of ribosome-bound mRNAs in the retinal ganglion cell axons of the developing and adult retinotectal projection in vivo. The embryonic-to-postnatal axonal translatome comprises an evolving subset of enriched genes with axon-specific roles suggesting distinct steps in axon wiring, such as elongation, pruning and synaptogenesis. Adult axons, remarkably, have a complex translatome with strong links to axon survival, neurotransmission and neurodegenerative disease. Translationally co-regulated mRNA subsets share common upstream regulators, and novel sequence elements generated by alternative splicing that promote axonal mRNA translation. Our results indicate that intricate regulation of compartment-specific mRNA translation in mammalian CNS axons supports the formation and maintenance of neural circuits in vivo. Overall design: The profiling of ribosome-bound mRNAs in mouse retinal ganglion cell axons at 4 different developmental stages
Publication Title
On-Site Ribosome Remodeling by Locally Synthesized Ribosomal Proteins in Axons.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Evaluation of specific coordinated pattern of transcriptional events consistent with anti-myeloma activity of FK866 (chemical Nampt inhibitor)
Publication Title
Targeting NAD+ salvage pathway induces autophagy in multiple myeloma cells via mTORC1 and extracellular signal-regulated kinase (ERK1/2) inhibition.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 27 Downloadable Samples
- Illumina HiSeq 2500
Description
The Polycomb Repressive Complex 2 (PRC2) is composed of core subunits SUZ12, EED, RBBP4/7 and EZH1/2, which together are responsible for all di- and tri- methylation of lysine 27 on Histone H3 (H3K27me2/3) in higher eukaryotes. While two distinct forms, PRC2.1 (containing one Polycomb-like protein) and PRC2.2 (containing AEBP2 and JARID2) exist, little is known about their differential functions or interplay. Here we report the discovery of a new family of vertebrate specific PRC2.1 associated proteins; 'PRC2 associated LCOR isoform 1' (PALI1) and PALI2, encoded by the LCOR and LCORL gene loci, respectively. PALI1 promotes PRC2 methyltransferase activity in vitro and in vivo and is essential for mouse development. We uncover an antagonistic relationship between the PALI-PRC2.1 and AEBP2-PRC2.2 subtypes and establish that both are required for balanced regulation of Polycomb target genes during differentiation. This discovery links the Polycomb epigenetic system with co-repressors and nuclear receptors in the regulation of cellular identity. Overall design: RNA seq analysis of Pali WT, Pali1 KO, Pali1/2 double KO, C129 WT and Aebp2 gene trap mouse embryonic stem cells at three time points (Day 0, Day 4 and Day 8) during embryoid body differentiation (EB). 30 samples are included. Biological duplicates are present.
Publication Title
A Family of Vertebrate-Specific Polycombs Encoded by the LCOR/LCORL Genes Balance PRC2 Subtype Activities.
Sample Metadata Fields
Specimen part, Subject
View Samples- Arabidopsis thaliana
- 15 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We generated single and double knockouts of AtNHX5 and AtNHX6 in order to invesigate possible functions in Arabidopsis. nhx5/nhx6 exhibited severe growth retardation related to cell size and proliferation, as well as endosomal trafficking perutrbations. The results implicate endosomal NHX antiporters in novel cellular functions. In order to investigate further the possible functions of AtNHX5 and AtNHX6, we compared the transcrptional profiles of single and double AtNHX5 and AtNHX6 knockouts. We looked for changes in gene expression might help us to elucidate the molecular events associated with the apparent requirement of AtNHX5 and AtNHX6 for normal growth and development.
Publication Title
The Arabidopsis intracellular Na+/H+ antiporters NHX5 and NHX6 are endosome associated and necessary for plant growth and development.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The exposure to and contamination by Persistent Organic Pollutants (POPs), which include pesticides used worldwide and polyaromatic hydrocarbons, is detrimental to human health and diverse ecosystems. Although most mechanistic studies have focused on single compounds, living organisms are exposed to multiple environmental xenobiotics, simultaneously, throughout their lives. The experimental evidence useful for assessing the effects of exposure to pollutant mixtures is scarce. We investigated the effects of exposure to a combination of two POPs, which employ different xenosensors, on global gene expression in a human hepatocyte cell model, HepaRG.
Publication Title
Two persistent organic pollutants which act through different xenosensors (alpha-endosulfan and 2,3,7,8 tetrachlorodibenzo-p-dioxin) interact in a mixture and downregulate multiple genes involved in human hepatocyte lipid and glucose metabolism.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Despite substantial investments, tuberculosis remains one of the biggest challenges in public health.
Publication Title
Synergy of chemotherapy and immunotherapy revealed by a genome-scale analysis of murine tuberculosis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Zidovudine remains the cornerstone drug for prophylaxis to prevent mother-to-child HIV-1 transmission. A mild but long-lasting hematological multilineage defect is observed in children exposed in utero.
Publication Title
Genotoxic signature in cord blood cells of newborns exposed in utero to a Zidovudine-based antiretroviral combination.
Sample Metadata Fields
Specimen part, Treatment
View Samples