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SRP052229
Homo sapiens
42 Downloadable Samples
IlluminaHiSeq2000
Description
Roberts syndrome (RBS) is a human developmental disorder caused by mutations in the cohesin acetyltransferase ESCO2. We previously reported that mTORC1 was inhibited and overall translation was reduced in RBS cells. Treatment of RBS cells with L-leucine partially rescued mTOR function and protein synthesis, correlating with increased cell division. In this study, we use RBS as a model for mTOR inhibition and analyze transcription and translation with ribosome profiling to determine genome-wide effects of L-leucine. The translational efficiency of many genes is increased with Lleucine in RBS cells including genes involved in ribosome biogenesis, translation, and mitochondrial function. snoRNAs are strongly upregulated in RBS cells, but decreased with L-leucine. Imprinted genes, including H19 and GTL2, are differentially expressed in RBS cells consistent with contribution to mTORC1 control. This study reveals dramatic effects of L-leucine stimulation of mTORC1 and supports that ESCO2 function is required for normal gene expression and translation. Overall design: 42 samples of human fibroblast cell lines with various genotypes (wt, corrected, and esco2 mutants) are treated with l-leucine or d-leucine (control) for 3 or 24 hours. Biological replicates are present.
Publication Title
Improved transcription and translation with L-leucine stimulation of mTORC1 in Roberts syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2), Affymetrix Mouse Expression 430A Array (moe430a)
Description
A microarray time series was generated to identify cyclic genes of the segmentation clock in the mouse. The right posterior half presomitic mesoderms (PSM) from 17 mouse embryos were dissected while the contralateral side of the embryo containing the left PSM was immediately fixed to be analyzed by in situ hybridization using a Lfng probe to order the samples along the segmentation clock oscillation cycle. Probes were produced from RNA extracted from the 17 dissected posterior half PSMs using a two-step amplification protocol and were hybridized to Affymetrix GeneChip MOE430A. The reproducibility of the amplification procedure was initially assessed by comparing array data generated from the right and the left posterior PSM from the same embryo. Because of the symmetry of the paraxial mesoderm along the left-right axis, left and right samples are expected to show overtly similar gene expression. RNA was amplified from three such sample pairs (1, a and b; 2, a and b; 3, a and b) and hybridized on Murine Genome U74Av2 array (MG-U74Av2)
Publication Title
A complex oscillating network of signaling genes underlies the mouse segmentation clock.
Sample Metadata Fields
Age, Specimen part, Subject, Time
View Samples- Mus musculus, Drosophila melanogaster
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Poised RNA polymerase II changes over developmental time and prepares genes for future expression.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Murine ES cell gene expression before RA induction are used to compare gene expression for time-points of 8, 12, 16, 24, 36, 48, 60 and 72 hours post-induction.
Publication Title
Poised RNA polymerase II changes over developmental time and prepares genes for future expression.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Drosophila melanogaster
- 13 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Poised RNA polymerase II is predominantly found at developmental control genes and is thought to allow their rapid and synchronous induction in response to extracellular signals. How the recruitment of poised RNA Pol II is regulated during development is not known. By isolating muscle tissue from Drosophila embryos at five stages of differentiation, we show that the recruitment of poised Pol II occurs at many genes de novo and this makes them permissive for future gene expression. When compared to other tissues, these changes are stage-specific and not tissue-specific. In contrast, Polycomb group repression is tissue-specific and in combination with Pol II (the balanced state) marks genes with highly dynamic expression. This suggests that poised Pol II is temporally regulated and is held in check in a tissue-specific fashion. We compare our data to mammalian embryonic stem cells and discuss a framework for predicting developmental programs based on chromatin state. Overall design: mRNA-seq of Drosophila tissues during development
Publication Title
Poised RNA polymerase II changes over developmental time and prepares genes for future expression.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mice that are mutant for both Fgfr1 and Fgfr2 specifically in the developing retina develop coloboma. To analyze the transcripts that are affected by defective FGF signaling, we micro-dissected the optic fissure region from the control and FGFR condtional mutant mice and did microarray analysis.
Publication Title
Defective FGF signaling causes coloboma formation and disrupts retinal neurogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The object of this study was to identify genes transcriptionally upregulated and downregulated in response to Tcof1 haploin-sufficiency during mouse embryogensis
Publication Title
Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Classically activated (M1) macrophages protect from infection but can cause inflammatory disease and tissue damage while alternatively activated (M2) macrophages reduce inflammation and promote tissue repair. Modulation of macrophage phenotype may be therapeutically beneficial and requires further understanding of the molecular programs that control macrophage differentiation. A potential mechanism by which macrophages differentiate may be through microRNA (miRNA), which bind to messenger RNA and post-transcriptionally modify gene expression, cell phenotype and function. The inflammation-associated miRNA, miR-155, was rapidly up-regulated over 100-fold in M1, but not M2, macrophages. Inflammatory M1 genes and proteins iNOS, IL-1b and TNF-a were reduced up to 72% in miR-155 knockout mouse macrophages, but miR-155 deficiency did not affect expression of genes associated with M2 macrophages (e.g., Arginase-1). Additionally, a miR-155 oligonucleotide inhibitor efficiently suppressed iNOS and TNF-a gene expression in wild-type M1 macrophages. Comparative transcriptional profiling of unactivated (M0) and M1 macrophages derived from wild-type and miR-155 knockout (KO) mice revealed an M1 signature of approximately 1300 genes, half of which were dependent on miR-155. Real-Time PCR of independent datasets validated miR-155's contribution to induction of iNOS, IL-1b, TNF-a, IL-6 and IL-12, as well as suppression of miR-155 targets Inpp5d, Tspan14, Ptprj and Mafb. Overall, these data indicate that miR-155 plays an essential role in driving the differentiation and effector potential of inflammatory M1 macrophages.
Publication Title
Control of the Inflammatory Macrophage Transcriptional Signature by miR-155.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 4000
Description
Purpose:We have the first-reported set of glial-specific transcripts utilizing the Ribotag model. We use this model to explore glial changes in DNBS-induced inflammation and neurokinin-2 receptor (NK2R) antagonism. Methods: Actively translated mRNA profiles of the distal colon myeneteric plexi of Rpl22(+/-)Sox10(+/-) male and female mice 8-10 weeks old were obtained utilizing the HA-tagged ribosomal immunoprecipitation and downstream RNA extraction. Samples meeting RNA quality standards by 18S and 28S rRNA peaks by 2100 Bioanalyzer and RNA 6000 Nano LabChip Kit (Agilent) were deep sequenced with the Illumina HiSeq 4000. Results: We mapped approximately 30-50 millions reads per sample to the mouse genome (v88) and identified approximately 100K ribosome-associated transcripts, with Tuxedo workflow, in distal colon glial cells with DNBS-induced inflammation and NK2R antagonism and their respective controls. Of these transcripts, changes in biological processes associated with inflammation and other important enteric nervous system communications between samples have been identified. Conclusions: Our study demonstrates the first use of the Ribotag model to provide glial cell-specific actively-translated mRNA changes in DNBS-induced inflammation with and without functional NK2R signalling. Overall design: Distal colon glial mRNA samples from Ribotag Rpl22(+/-)Sox10(+/-) mice administered either saline or DNBS and DMSO vehicle or NK2R antagonism.
Publication Title
Communication Between Enteric Neurons, Glia, and Nociceptors Underlies the Effects of Tachykinins on Neuroinflammation.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: To understand the molecular mechanisms underlying NPM1c-mediated tumorigenesis by comparing the transcriptome of de novo generated bulk human leukemic cells and leukemic stem cells Overall design: Human hematopoietic stem/progenitor cells (HSPC) are transduced with lentiviruses expressing a mutated form of Nucleophosmin (NPM1c). Following engraftment into immunodeficient mice, transduced HSPCs give rise to human myeloid leukemia whereas untransduced HSPCs give rise to human immune cells in the same mice. The de novo AML, with CD123+ leukemic stem cells (LSC), resembles NPM1c+ AML from patients.
Publication Title
Induction and Therapeutic Targeting of Human NPM1c<sup>+</sup> Myeloid Leukemia in the Presence of Autologous Immune System in Mice.
Sample Metadata Fields
Specimen part, Subject
View Samples