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Homo sapiens
8 Downloadable Samples
Illumina HiSeq 2000
Description
Huge efforts are made to engineer safe and efficient genome editing tools. An alternative might be the harnessing of ADAR-mediated RNA editing. We now present the engineering of chemically optimized antisense oligonucleotides that recruit endogenous human ADARs to edit endogenous transcripts in a simple and programmable way, an approach we refer to as RESTORE. Notably, RESTORE was markedly precise, and there was no evidence for perturbation of the natural editing homeostasis. We applied RESTORE to a panel of standard human cell lines, but also to several human primary cells including hepatocytes. In contrast to other RNA and DNA editing strategies, this approach requires only the administration of an oligonucleotide, circumvents the ectopic expression of proteins, and thus represents an attractive platform for drug development. In this respect we have shown the repair of the PiZZ mutation causing a1-antitrypsin deficiency and the editing of phosphotyrosine 701 in STAT1. Overall design: Identification of off-target editing events and Interferon-a influence in HeLa cell line transfected with an ASO for RNA editing by RNA-Seq, 2 samples (ASO +/- IFN) , 2 control sample (+/-IFN), 2 biologically independent experiments for each sample, 8 samples in total
Publication Title
Precise RNA editing by recruiting endogenous ADARs with antisense oligonucleotides.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Rattus norvegicus
- 39 Downloadable Samples
Affymetrix Rat Genome U34 Array (rgu34a)
Description
Although glucocorticoids (GCs) are known to exert numerous effects in the hippocampus, their chronic regulatory functions remain poorly understood. Moreover, evidence is inconsistent regarding the longstanding hypothesis that chronic GC exposure promotes brain aging/Alzheimer's disease. Here, we adrenalectomized male F344 rats at 15-months-of-age, maintained them for 3 months with implanted corticosterone (CORT) pellets producing low or intermediate (glucocorticoid-receptor (GR)-activating) blood levels of CORT, and performed microarray/pathway analyses in hippocampal CA1. We defined the chronic GC-dependent transcriptome as 393 genes that exhibited differential expression between Intermediate- and Low-CORT groups. Short-term CORT (4 days) did not recapitulate this transcriptome. Functional processes/pathways overrepresented by chronic CORT-upregulated genes included learning/plasticity, differentiation, glucose metabolism and cholesterol biosynthesis, whereas processes overrepresented by CORT-downregulated genes included inflammatory/immune/glial responses and extracellular structure. These profiles indicate that GCs chronically activate neuronal/metabolic processes while coordinately repressing a glial axis of reactivity/inflammation. We then compared the GC-transcriptome with a previously-defined hippocampal aging transcriptome, revealing a high proportion of common genes. Although CORT and aging moved expression of some common genes in the same-direction, the majority were shifted in opposite directions by CORT and aging (e.g., glial inflammatory genes downregulated by CORT are upregulated with aging). These results contradict the hypothesis that GCs simply promote brain aging, and also suggest that the opposite-direction shifts during aging reflect resistance to CORT regulation. Therefore, we propose a new model in which aging-related GC resistance develops in some target pathways while GC overstimulation develops in others, together generating much of the brain aging phenotype.
Publication Title
Glucocorticoid-dependent hippocampal transcriptome in male rats: pathway-specific alterations with aging.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This study characterizes the response of primary human endothelial cells (human umbilical vein endothelial cells, HUVECs) to the relative shear stress changes that occur during the initiation of arteriogenesis at the entrance regions to a collateral artery network. HUVECs were preconditioned to a baseline level of unidirectional shear of 15 dynes/cm2 for 24 hours. After 24 hours preconditioning, HUVECs were subjected to an arteriogenic stimulus that mimics the shear stress changes observed in the opposing entrance regions into a collateral artery network. The arteriogenic stimulus consisted of a 100% step wise increase in shear stress magnitude to a unidirectional 30 dynes/cm2 in either the same or opposite direction of the preconditioned shear stress. This simulates either the feeding entrance to the collateral artery circuit or the region that drains into the vasculature downstream of an obstruction in a major artery, respectively. In vivo analysis of collateral growth in the mouse hindlimb showed enhanced outward remodeling in the re-entrant (direction reversing) region that reconnects to the downstream arterial tree, suggesting reversal of shear stress direction as a key enhancer of arteriogenesis. Transcriptional profiling using microarray techniques identified that the reversal of shear stress direction, but not an increase in shear stress alone, yielded a broad-based enhancement of the mechanotransduction pathways necessary for the induction of arteriogenesis.
Publication Title
Mechanisms of Amplified Arteriogenesis in Collateral Artery Segments Exposed to Reversed Flow Direction.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 8 Downloadable Samples
- Illumina mouseRef-8 v1.1 expression beadchip
Description
GATA factors interact with simple DNA motifs (WGATAR) to regulate critical processes, including hematopoiesis, but very few WGATAR motifs are occupied in genomes. Given the rudimentary knowledge of mechanisms underlying this restriction, and how GATA factors establish genetic networks, we used ChIP-seq to define GATA-1 and GATA-2 occupancy genome-wide in erythroid cells. Coupled with genetic complementation analysis and transcriptional profiling, these studies revealed a rich collection of targets containing a characteristic binding motif of greater complexity than WGATAR. GATA factors occupied loci encoding multiple components of the Scl/TAL1 complex, a master regulator of hematopoiesis and leukemogenic target. Mechanistic analyses provided evidence for cross-regulatory and autoregulatory interactions among components of this complex, including GATA-2 induction of the hematopoietic corepressor ETO-2 and an ETO-2 negative autoregulatory loop. These results establish fundamental principles underlying GATA factor mechanisms in chromatin and illustrate a complex network of considerable importance for the control of hematopoiesis.
Publication Title
Discovering hematopoietic mechanisms through genome-wide analysis of GATA factor chromatin occupancy.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina mouseRef-8 v1.1 expression beadchip
Description
Total RNA was analyzed from either uninduced or -estradiol treated G1E-ER-GATA cells to determine changes in gene expression upon induction of erythroid maturation (treated).
Publication Title
Discovering hematopoietic mechanisms through genome-wide analysis of GATA factor chromatin occupancy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 202 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Background: Mycobacterium tuberculosis infection is a leading cause of infectious death worldwide. Gene-expression microarray studies profiling the blood transcriptional response of tuberculosis (TB) patients have been undertaken in order to better understand the host immune response as well as to identify potential biomarkers of disease. To date most of these studies have focused on pulmonary TB patients with gene-expression profiles of extra-pulmonary TB patients yet to be compared to those of patients with pulmonary TB or sarcoidosis.
Publication Title
The Transcriptional Signature of Active Tuberculosis Reflects Symptom Status in Extra-Pulmonary and Pulmonary Tuberculosis.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Race
View Samples
GSE35516- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Hepatocyte-specific mutation of both NF-κB RelA and STAT3 abrogates the acute phase response in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
A common response to physiological duress is the hepatic acute phase response, a process during which the expression of many genes is altered in the liver. Amongst these transcripts are those encoding acute phase proteins, defined as circulating proteins with significantly changed concentrations during an acute phase response. The goal of this study was to determine the influence of two transcription factors, STAT3 and NF-kappaB p65 (RelA), on hepatic gene changes including but not limited to acute phase proteins during bacterial pneumonia.
Publication Title
Hepatocyte-specific mutation of both NF-κB RelA and STAT3 abrogates the acute phase response in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
A common response to physiological duress is the hepatic acute phase response, a process during which the expression of many genes is altered in the liver. Amongst these transcripts are those encoding acute phase proteins, defined as circulating proteins with significantly changed concentrations during an acute phase response. The goal of this study was to determine the influence of NF-kappaB RelA (p65) on hepatic gene changes including but not limited to acute phase proteins during bacterial pneumonia.
Publication Title
Hepatocyte-specific mutation of both NF-κB RelA and STAT3 abrogates the acute phase response in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
A common response to physiological duress is the hepatic acute phase response, a process during which the expression of many genes is altered in the liver. Amongst these transcripts are those encoding acute phase proteins, defined as circulating proteins with significantly changed concentrations during an acute phase response. The goal of this study was to determine the influence of STAT3 on hepatic gene changes including but not limited to acute phase proteins during bacterial pneumonia.
Publication Title
Hepatocyte-specific mutation of both NF-κB RelA and STAT3 abrogates the acute phase response in mice.
Sample Metadata Fields
Specimen part
View Samples