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SRP045378
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2500
Description
Methods: CaMKIIa-creERT2 (Erdmann et al., 2007) and Dicer1f/f (Harfe et al., 2005) were crossed to produce inducible forebrain-restricted Dicer1 knockout mice (Dicer-ifKO) mice. Hippocampal mRNA profiles of 3-month-old wild-type (WT) and (Dicer-ifKO) mice were generated by deep sequencing, in triplicate, using Illumina HiSeq 2500. Each sample included total RNA isolated from the hippocampus of 3 mice. In total, 12 mice per genotype were used. The sequence reads that passed quality filters were mapped to reference genome (GRCm38/mm10) using Bowtie 2 (2.0.5) and TopHat (2.0.6). SAM/BAM files were further processed with Samtools (0.1.18). Read count quantitations were obtained using Seqmonk (0.26.0). Normalization of read counts and differential expression analysis between genotypes was carried out using DESeq2 R package from Bioconductor (Release 2.13). qRT–PCR validation was performed using SYBR Green assays. Results: We mapped about 13-14 million sequence reads per sample to the mouse genome (build GRCm38/mm10) and quantified 76,938 annotated transcripts. DESeq2 R package was used to normalize the counts and perform the differential expression. Differential analysis output was filtered by FDR threshold (padj < 0.1). This approach led us to identify 641 gene isoforms, corresponding to 314 genes that were differentially regulated in the mouse hippocampus upon Dicer ablation. Conclusions: We extend here the characterization of inducible forebrain-restricted Dicer1 mutants confirming the initial memory improvement. Moreover, we describe several novel phenotypes associated with early Dicer loss in the mature brain including an exacerbated response to seizures, increased CA1 neuron excitability, a pronounced weight gain and enhanced induction of immediate early genes (IEGs) in relevant neuronal nuclei. To identify candidate genes that could explain these phenotypes, we conducted two complementary genomic screens for the miRNAs primarily affected and their targets. Overall, our results explain both the initial and late consequences of Dicer loss in excitatory neurons and indicate that Dicer and the miRNA system play a critical role regulating neuronal homeostasis and responsiveness. Overall design: Hippocampal mRNA profiles of 3-month-old wild-type (WT) and Dicer-ifKO (3 weeks upon tamoxifen administration) male mice were generated by deep sequencing, in triplicate, using Illumina HiSeq 2500. Each sample included total RNA isolated from the hippocampus of 3 mice. In total, 12 mice per genotype were used.
Publication Title
Blocking miRNA Biogenesis in Adult Forebrain Neurons Enhances Seizure Susceptibility, Fear Memory, and Food Intake by Increasing Neuronal Responsiveness.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
ATFS-1 has been shown to regulate transcription of mitochondrial chaperone genes such as mtHsp70/hsp-6 and hsp-60 in response to mitocondrial stress. To identify the entire ATFS-1-mediated response, we compared the transcript profiles from wild-type and atfs-1(tm4525) worms raised in the absence and presence of mitochondrial stress.
Publication Title
Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Illumina HiSeq 2500, NextSeq 500
Description
Samples 1-4 report RNA-seq transcriptome profiling of the L-Proline- (L-Pro) and bFgf/ActivinA- (F/A) derived mCherry+/eGFP+ (yellow) ESC population, using the Illumina HiSeq platform. Whole-genome expression revealed that more than 1000 genes were significantly deregulated in L-Pro- and F/A-induced cells compared to control (mCherry+/eGFP- red cells) and the two population shared up to 75% of deregulated genes with the same deregulation trend. Specifically, the pluripotency-associated genes were downregulated either at similar level (Nanog, Klf2, Klf4 and Gbx2) or at lower levels (up to 10 times) (Dppa 2, 3, 4, 5a, Rex1, Esrrb) in F/A- compared to L-Pro-treated cells. Interestingly, mesendodermal-related genes (e.g. Brachyury, Cer1, Dkk1, Eomes, Foxa2, and Sox17) were induced in both conditions but at significant higher levels in F/A- compared to L-Pro-treated cells. The transcriptome analysis of mCherry+/eGFP+ (yellow) cells supported the idea that L-Pro mimics F/A in inducing a naïve to primed transition, and suggested that it exerted a milder (weaker) effect. Samples 5-14 report RNA-seq transcriptome profiling of the mir-290_mCherry/mir-302_eGFP dual reporter ESCs (DRESCs) bulk culture, grown in FBS/LIF ± VitaminC (VitC) and L-Proline (L-Pro) and compared them to the standard naive/2i and primed/bFgf/ActivinA-EpiSCs (F/A), using the Illumina HiSeq platform. Whole-genome expression identified around 7900 deregulated genes in the different conditions, (fold change=2 and pvalue<0.05). Principal component analysis (PCA) placed VitC between 2i and untreated control, and L-Pro between control and F/A. Accordingly, a set of pluripotency-associated genes was expressed at higher level in 2i and VitC conditions, while downregulated in L-Pro and F/A, compared to control. Conversely, priming markers were downregulated in 2i and VitC and upregulated in L-Pro and F/A compared to control The transcriptome analysis supported that VitC- and L-Pro captured alternative pluripotency states that can be likely placed between naïve/2i and primed/F/A states. Overall design: RNA-seq profiling of ESCs grown in FBS/LIF ± VitC, 2i, L-Pro or F/A, using the Illumina HiSeq platform
Publication Title
Vitamin C and l-Proline Antagonistic Effects Capture Alternative States in the Pluripotency Continuum.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Tcl1 is known to be involved in survival, proliferation and differentiation of human lymphocytes and mouse embryonic stem cells. Loss of Tcl1 gene in the KO mouse model affects skin integrity inducing alopecia and ulcerations.
Publication Title
T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 35 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We measured gene expression across the whole genome in a panel of lines selected for a wing shape trait (angular offset). The lines were created in separate experiments, originating from two widely separated populations, and including multiple replicates of one population, but all were created using the same selection regime and trait. Here we evaluate the data with two objectives: 1) to identify candidate wing shape genes for future testing and validation, and 2) to assess variation among lines in the outcome of identical selection regimes
Publication Title
Microarray analysis of replicate populations selected against a wing-shape correlation in Drosophila melanogaster.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Androgen receptor (AR) is a ligand-dependent transcription factor that plays a key role in the onset and progression of prostate cancer. We investigated AR-induced gene expression in prostate cancer cells LNCaP and abl by transfecting siAR / siControl or treating cells with androgen (DHT) over a time course.
Publication Title
Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression profiling of normal hematopoietic cell subpopulations
Publication Title
Gene expression signatures in childhood acute leukemias are largely unique and distinct from those of normal tissues and other malignancies.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to detail the global program of gene expression underlying the effect of p17 on human plasmacytoid dendritic cells and was compared to CpG profile.
Publication Title
HIV-1 matrix protein p17 induces human plasmacytoid dendritic cells to acquire a migratory immature cell phenotype.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Saccharomyces cerevisiae
- 83 Downloadable Samples
- Illumina HiSeq 2500, Illumina HiSeq 2000, Illumina Genome Analyzer IIx
Description
Purpose: The ability to rationally manipulate the transcriptional states of cells would be of great use in medicine and bioengineering. We have developed a novel algorithm, NetSurgeon, which utilizes genome-wide gene regulatory networks to identify interventions that force a cell toward a desired expression state. Results: We used NetSurgeon to select transcription factor deletions aimed at improving ethanol production in S. cerevisiae cultures that are catabolizing xylose. We reasoned that interventions that move the transcriptional states of cells utilizing xylose toward the fermentative state typical of cells that are producing ethanol rapidly (while utilizing glucose) might improve xylose fermentation. Some of the interventions selected by NetSurgeon successfully promoted a fermentative transcriptional state in the absence of glucose, resulting in strains with a 2.7-fold increase in xylose import rates, a 4-fold improvement in xylose integration into central carbon metabolism, or a 1.3-fold increase in ethanol production rate. Conclusions: We conclude by presenting an integrated model of transcriptional regulation and metabolic flux that will enable future metabolic engineering efforts aimed at improving xylose fermentation to prioritize functional regulators of central carbon metabolism. Overall design: Mutant and wildtype S. cerevisiae cells were put into 48 hour aerobic batch fermentations of synthetic complete medium supplmented with 2% glucose and 5% xylose and culture samples were taken at 4 hours and 24 hours for transcriptional profiling performed by RNA-Seq analysis. In addition, wildtype S. cerevisiae cells were grown in various single carbon sources for 12 hours and culture samples were taken for transcriptional profiling performed by RNA-Seq analysis.
Publication Title
Model-based transcriptome engineering promotes a fermentative transcriptional state in yeast.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 85 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Human brown fat tumors (hibernomas) display concomitant loss of the tumor suppressor genes MEN1 and AIP. In the present study, we hypothesized that the brown fat phenotype is attributed to these mutations. Accordingly, we demonstrate that silencing of AIP in human brown preadipocytic and white fat cell lines results in the induction of the brown fat marker UCP1. In human adipocytic tumors, loss of MEN1 was found both in white (one out of 51 lipomas) and brown fat tumors. In contrast, concurrent loss of AIP was always accompanied by a brown fat morphology. We conclude that this white-to-brown phenotype switch in brown fat tumors is mediated by the loss of AIP.
Publication Title
Loss of the tumour suppressor gene AIP mediates the browning of human brown fat tumours.
Sample Metadata Fields
Specimen part
View Samples