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SRP058702
Mus musculus
12 Downloadable Samples
Illumina HiSeq 2000
Description
The cellular and molecular aspects of post-infarct left-ventricle remodeling in presence of type-2 diabetes is poorly understood. In this study we have addressed the cellular and molecular aspects underlying post-infarct left-ventricle remodeling in type 2 diabetic (T2DM) mice using genome-wide mRNA-sequencing. Myocardial infarction was induced by ligating left-anterior descending artery (LAD) in 12-14 month old T2DM and control mice. Cardiac MRI was performed at baseline, day 7 and 14 post-LAD ligation. Blood and tissue samples were collected for biochemical and immunohistochemical, molecular biology analysis after sacrification at day 7 and 14. Genome-wide mRNA sequencing analysis was performed from left-ventricular tissues collected at day 7 post-LAD ligation. Mitochondrial dynamics, Leukocyte recruitment and Collagen I deposition were analyzed using electron microscopy, fluorescent assisted cell sorting (FACS) and fourier-transform infra-red (FTIR) spectroscopy from left ventricular tissues collected at day 7 and 14 post-LAD ligation. Cardiac ejection fraction (EF) and stroke volume (SV) were significantly reduced along with increased mortality in T2DM compared to controls. Ingenuity pathway analyses of differentially expressed genes were enriched for mitochondrial dysfunction, TCA cycle and fatty acid oxidation. Additionally, upstream transcription factor analysis showed inhibition of PGC1a, PGC1b, ESRRA, ESRRB and TFAM in infarcted myocardium of T2DM mice. Electron microscopy analysis showed an altered mitochondrial dynamics and cardiomyocyte death in ischemic myocardium of T2DM mice. Leukocytes exhibited an altered phenotype in ischemic myocardium of T2DM mice. Neovascularization was impaired and collagen deposition was increased in ischemic myocardium of T2DM mice. We conclude that an altered mitochondrial dynamics, cell death modalities, leukocyte phenotype, neovascularization responses and fibrosis may contribute to an increased mortality after myocardial infarction in T2DM. Modulation of mitochondrial dynamics and cardiomyocyte cell death modalities may offer a novel therapeutic target. Overall design: Myocardial infarction was induced by ligating left anterior descending artery (LAD). Total RNA was isolated from remote, Infarct and border zones at day 7 after myocardial infarction. Poly (A)+RNA fraction was subjected to RNA sequencing using Illumina HiSeq.
Publication Title
Aggravated Postinfarct Heart Failure in Type 2 Diabetes Is Associated with Impaired Mitophagy and Exaggerated Inflammasome Activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 96 Downloadable Samples
- NextSeq 500
Description
The pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for vertebrate development. A range of genomic analyses, including: mNET-seq, 3' mRNA-seq, chromatin RNA-seq and ChIP-seq, reveals that PCF11 enhances transcription termination and stimulates early polyadenylation genome-wide. PCF11 binds preferentially between closely spaced genes, where it prevents transcriptional interference and downstream gene silencing. Notably, PCF11 is sub-stoichiometric to the CPA complex. Low levels of PCF11 are maintained by an auto-regulatory mechanism involving premature termination of its own transcript, and are important for normal development. Both in human cell culture and during zebrafish development, PCF11 selectively attenuates the expression of other transcriptional regulators by premature CPA and termination. Overall design: Semi-nascent transcriptome measured by chromatin-bound RNA-seq in HeLa cells. Control and PCF11 knock-down (2 biological replicates) and control and PCF11 PAS1 deletion (4 biological replicates).
Publication Title
Selective Roles of Vertebrate PCF11 in Premature and Full-Length Transcript Termination.
Sample Metadata Fields
Specimen part, Subject
View Samples- Danio rerio
- 56 Downloadable Samples
- Illumina HiSeq 2500
Description
The pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for vertebrate development. A range of genomic analyses, including: mNET-seq, 3' mRNA-seq, chromatin RNA-seq and ChIP-seq, reveals that PCF11 enhances transcription termination and stimulates early polyadenylation genome-wide. PCF11 binds preferentially between closely spaced genes, where it prevents transcriptional interference and downstream gene silencing. Notably, PCF11 is sub-stoichiometric to the CPA complex. Low levels of PCF11 are maintained by an auto-regulatory mechanism involving premature termination of its own transcript, and are important for normal development. Both in human cell culture and during zebrafish development, PCF11 selectively attenuates the expression of other transcriptional regulators by premature CPA and termination. Overall design: 3' mRNA-seq in individual zebrafish embryo heads. Two types of mutants: zPCF11 null and zPCF11 with deletion of PAS1. Wild-type (wt, +/+), heterozygous (het, +/-) and homozygous mutant (hom, -/-) embryos were analyzed. Wild-type and heterozygous animals were phenotypically indistinguishable.
Publication Title
Selective Roles of Vertebrate PCF11 in Premature and Full-Length Transcript Termination.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
- Illumina HiSeq 2500
Description
The pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for vertebrate development. A range of genomic analyses, including: mNET-seq, 3' mRNA-seq, chromatin RNA-seq and ChIP-seq, reveals that PCF11 enhances transcription termination and stimulates early polyadenylation genome-wide. PCF11 binds preferentially between closely spaced genes, where it prevents transcriptional interference and downstream gene silencing. Notably, PCF11 is sub-stoichiometric to the CPA complex. Low levels of PCF11 are maintained by an auto-regulatory mechanism involving premature termination of its own transcript, and are important for normal development. Both in human cell culture and during zebrafish development, PCF11 selectively attenuates the expression of other transcriptional regulators by premature CPA and termination. Overall design: 3' mRNA-seq in HeLa cells. Control and PCF11 knock-down (4 biological replicates); control and PCF11 PAS1 deletion clones muA and muB (3 biological replicates); control and additional PCF11 PAS1 deletion clones muC and muD (1 replicate).
Publication Title
Selective Roles of Vertebrate PCF11 in Premature and Full-Length Transcript Termination.
Sample Metadata Fields
Subject
View Samples- Arabidopsis thaliana
- 20 Downloadable Samples
Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Tissues of Arabidopsis plants overexpressing artificial microRNAs were compared to wild_type and respective target gene mutants (duplicate arrays)
Publication Title
Highly specific gene silencing by artificial microRNAs in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The pre-synaptic protein -synuclein is a key player in the pathogenesis of Parkinson's disease. Together with accumulation and missfolding of -synuclein protofibrils serve as seed structures for the aggregation of numerous proteins in the cytoplasm of neuronal cells, the so-called Lewy bodies. Furthermore, missense mutations in the SNCA gene and gene multiplications lead to autosomal dominant forms of familiar PD. However, so far the exact biological role of -synuclein in normal brain is elusive. To gain more insights into the biological function of this protein we monitored whole genome expression changes in dopaminergic neuroblastoma cells (SH-SY5Y) caused by a 90% reduction of -synuclein by RNA interference.
Publication Title
Microarray expression analysis of human dopaminergic neuroblastoma cells after RNA interference of SNCA--a key player in the pathogenesis of Parkinson's disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 415 Downloadable Samples
- Illumina HiSeq 2500
Description
SMART-seq2 was performed on single cells isolated from visually staged zebrafish embryos. Overall design: Samples were all sequenced in one batch. Some were generated with a 5'' UMI-tagged method, and others are full-length SMART-seq2.
Publication Title
Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis.
Sample Metadata Fields
Subject
View Samples- Mus musculus, Homo sapiens
- 30 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Danio rerio
- 28 Downloadable Samples
- NextSeq 500
Description
Wild-type zebrafish embryos were mechanically dissociated and profiled using Drop-seq Overall design: Drop-seq was performed on 28 groups of 20-40 visually staged, mechanically dissociated embryos. Samples were combined and sequenced in batches DS2-DS5.
Publication Title
Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- IlluminaHiSeq2500
Description
Substantial effort is currently devoted to identifying cancer-associated alterations using genomics. Here, we show that standard blood collection procedures rapidly change the transcriptional and post-transcriptional landscapes of hematopoietic cells, resulting in biased activation of specific biological pathways, up-regulation of pseudogenes, antisense RNAs, and unannotated coding isoforms, and RNA surveillance inhibition. Affected genes include common mutational targets and thousands of other genes participating in processes such as chromatin modification, RNA splicing, T and B cell activation, and NF-?B signaling. The majority of published leukemic transcriptomes exhibit signals of this incubation-induced dysregulation, explaining up to 40% of differences in gene expression and alternative splicing between leukemias and reference normal transcriptomes. The effects of sample processing are particularly evident in pan-cancer analyses. We provide biomarkers that detect prolonged incubation of individual samples, and show that keeping blood on ice markedly reduces changes to the transcriptome. In addition to highlighting the potentially confounding effects of technical artifacts in cancer genomics data, our study emphasizes the need to survey the diversity of normal as well as neoplastic cells when characterizing tumors. This study is complemented by GSE61410: transcriptomic profiling of bone marrow cells from healthy individuals. Overall design: Peripheral blood mononuclear cells (PBMCs) were isolated from four healthy individuals, following an ex vivo incubation of variable length at either room temperature or on ice. RNA transcriptomes were measured using the Illumina HiSeq.
Publication Title
Sample processing obscures cancer-specific alterations in leukemic transcriptomes.
Sample Metadata Fields
No sample metadata fields
View Samples