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GSE99926
Homo sapiens
91 Downloadable Samples
Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
GGF2 is a recombinant human neuregulin-1 in development for chronic heart failure. Phase 1 clinical trials of GGF2 were put on hold when transient elevations in serum aminotransferases and total bilirubin were observed in 2 of 43 subjects receiving GGF2. However, aminotransferase elevations were modest and not typical of liver injury sufficient to result in elevated serum bilirubin. Several translational approaches were used to understand the liver response associated with GGF2.
Publication Title
Transient Changes in Hepatic Physiology That Alter Bilirubin and Bile Acid Transport May Explain Elevations in Liver Chemistries Observed in Clinical Trials of GGF2 (Cimaglermin Alfa).
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
Description
MicroRNAs have been implicated in the molecular pathogenesis of calcineurin inhibitor nephrotoxicity. However, identification of bona fide physiologically relevent miRNA/mRNA targeting interactions remains a challenge. To define a comprehensive miRNA/mRNA targetome and determine the role of miRNAs in cyclsporine-induced nephrotoxicity, we performed PAR-CLIP (Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation) against endogenous Argonaute 2 (AGO2) protein in human proximal tubule cells treated with cyclosporine A (CsA) or vehicle control. Statistically significant mRNA targets of miRNAs in the RNA Inducing Silencing Complex (RISC) complex were identified by PIPE-CLIP, a bioinformatic framework based on a zero-truncated negative binomial model. Further, we determined the total cellular differential expression of miRNAs and mRNAs by conventional deep sequencing methods. Our data indicate that CsA causes specific changes in miRNAs and mRNAs associated with the RISC complex. A relatively small fraction of the miRNAs and mRNAs identified by total cell RNA-seq were also found in the RISC complex suggesting that changes in targeting by miRs are not necessarily reflected in changes observed in total cellular RNA. Pathway enrichment analysis after integrating miRNA-seq, mRNA-seq, and PAR-CLIP datasets identified canonical pathways specifically under regulation by miRNAs following CsA treatment. Our analysis indicates that miRNAs play an integral role in regulating widespread dysregulation of the proximal tubule cell gene program, contributing to alterations in cell-cell adhesion, integrin-cytoskeleton signaling, and calcium signaling. Analysis of high confidence 3''UTR targets revealed a specific role for miR-101-3p in regulating MAPK signaling which may contribute to the pathogenesis of cyclosporine-induced nephrotoxicity in a calcineurin-independent manner. Overall design: AGO2-PAR-CLIP, mRNA-seq, and miRNA-seq of a human kidney proximal tubule cell line (HK-2) treated with cyclosporine A or vehicle control was performed and sequenced by Illumina HiSeq 2500. Two replicate AGO2-PAR-CLIP samples in each condition and four replicates in each condition for mRNA-seq and miRNA-seq were obtained.
Publication Title
Defining a microRNA-mRNA interaction map for calcineurin inhibitor induced nephrotoxicity.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 8 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Neuregulin-1 (NRG-1) is a paracrine factor critical for cardiac development. We have been examining whether the recombinant NRG-1 isoform known as glial growth factor 2 (GGF2) has therapeutic potential for heart failure. In both small and large animals after experimental myocardial infarction (MI) we have found that GGF2 treatment improves myocardial function and limits progressive myocardial remodeling. To understand potential mechanisms for this effect, we compared gene expression in swine by microarray analysis.
Publication Title
Anti-remodeling and anti-fibrotic effects of the neuregulin-1β glial growth factor 2 in a large animal model of heart failure.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Implications for neuroprotection in Parkinson's disease
Publication Title
VTA neurons show a potentially protective transcriptional response to MPTP.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The blockage of GABA-A ionotropic channels by means of gabazine is a widespread model of plasticity where the increased synaptic activity triggered by Gabazine leads to the up-regulation of a plethora of activity-dependent genes. Here, we sought to characterize the overall transcriptional response of GABA-A blocking of rat hippocampal organotypic cultures.
Publication Title
Early phase of plasticity-related gene regulation and SRF dependent transcription in the hippocampus.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Arabidopsis thaliana MYB80 (formerly MYB103) is expressed in the tapetum and microspores between anther developmental stages 6 and 10. MYB80 encodes a MYB transcription factor that is essential for tapetal and pollen development. In order to identify the genes regulated by MYB80, microarray technology was employed to analyze the expression levels of genes that were differentially regulated in the myb80 mutant and wild- type anthers.
Publication Title
The MYB80 transcription factor is required for pollen development and the regulation of tapetal programmed cell death in Arabidopsis thaliana.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
There is emerging evidence that, beyond their cholesterol lowering properties, statins exhibit important antileukemic effects in vitro and in vivo, but the precise mechanisms by which they generate such responses remain to be determined. We have previously shown that statins promote differentiation of acute promyelocytic leukemia (APL) cells and enhance generation of all-trans-retinoic acid (ATRA)-dependent antileukemic responses. We now provide evidence that statin-dependent leukemic cell differentiation requires engagement and activation of the JNK kinase pathway. In addition, in experiments to define the molecular targets and mediators of statin-induced differentiation we found a remarkable effect of statins on ATRA-dependent gene transcription, evidenced by the selective induction of over 400 genes by the combination of atorvastatin and ATRA. Altogether, our studies identify novel statin molecular targets linked to differentiation, establish that statins modulate ATRA-dependent transcription, and suggest that combined use of statins with retinoids may provide a novel approach to enhance antileukemic responses in APL and possibly other leukemias.
Publication Title
Regulation of leukemic cell differentiation and retinoid-induced gene expression by statins.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
mouse-6 v1.1 (Illumina), Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Feature Number version)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
HoxA3 is an apical regulator of haemogenic endothelium.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- mouse-6 v1.1 (Illumina)
Description
We used a murine ES cell line in which HoxA3 expression is under control of a tetracycline-responsive element and differentiated these cells as embryoid bodies (EBs). Endothelial (Flk-1 VE-cadherin double positive, FV) and hematopoieitc progenitors (c-Kit CD41 double positive, K41) were isolated from differentiated EBs that had been induced for 6 hours by doxycycline (Dox) treatment.
Publication Title
HoxA3 is an apical regulator of haemogenic endothelium.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 21 Downloadable Samples
- Illumina HiSeq 2000
Description
The ability to assign expression patterns to individual cell types that constitute a tissue is a major challenge in RNA expression analysis. This especially applies to brain given the plethora of different cells coexisting in that tissue. Here, we derived cell-type specific transcriptome signatures from existing single cell RNA data and integrated these signatures with a newly generated dataset of expression (bulk RNA-seq) of the postnatal developing hippocampus. This integrated analysis allowed us to provide a comprehensive and unbiased prediction of the differentiation drivers for 10 different hippocampal cell types and describe how the different cell types interact to support crucial developmental stages. Our integrated analysis provides a reliable resource of predicted differentiation drivers and insight into the multifaceted aspects of the cells in hippocampus during development. Overall design: 21 RNA-seq samples. For the stages E15, P1, P7, P15, and P30, there are respectively 3, 4, 3, 3, and 6 RNA-seq biological replica (total 19). One RNA-seq sample has two technical replica.
Publication Title
Integrated transcriptional analysis unveils the dynamics of cellular differentiation in the developing mouse hippocampus.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples