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SRP106651
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- 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- 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- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
p63 mutations have been associated with several human hereditary disorders characterized by ectodermal dysplasia such as EEC syndrome, ADULT syndrome and AEC syndrome . The location and functional effects of the mutations that underlie these syndromes reveal a striking genotype-phenotype correlation. Unlike EEC and ADULT that result from missense mutations in the DNA-binding domain of p63, AEC is solely caused by missense mutations in the SAM domain of p63. We report a study on the TAp63a isoform, the first to be expressed during development of the embryonic epithelia, and on its naturally occurring Q540L mutant derived from an AEC patient. To assess the effects of the Q540L mutation, we generated stable cell lines expressing TAp63a wt, DeltaNp63 alpha or the TAp63 alpha-Q540L mutant protein and used them to systematically compare the cell growth regulatory activity of the mutant and wt p63 proteins and to generate, by microarray analysis, a comprehensive profile of differential gene expression. We found that the Q540L substitution impairs the transcriptional activity of TAp63a and causes misregulation of genes involved in the control of cell growth and epidermal differentiation.
Publication Title
The Hay Wells syndrome-derived TAp63alphaQ540L mutant has impaired transcriptional and cell growth regulatory activity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
mRNA present in EPC derived microvescicles were detected using a RNA quantity curve, in order to evaluate if these vescicles were shuttling a specific subset of mRNAs
Publication Title
Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 87 Downloadable Samples
- Illumina HiSeq 3000, Illumina HiSeq 2500
Description
Mammalian genomes encode several hundred Krüppel-associated box zinc finger proteins (KRAB-ZFPs) that bind DNA in a sequence-specific manner through tandem arrays of C2H2-type zinc fingers and repress transcription via KRAB-dependent recruitment of the silencing cofactor KAP1. The KRAB-ZFP family rapidly amplified and diversified in mammals by segmental gene duplications, mutations, and zinc finger rearrangements likely in response to continued transposable element invasions, but the biological functions and in vivo requirement of these proteins has gone largely unexplored. We determined the genomic binding sites of 61 murine KRAB-ZFPs and genetically deleted five large KRAB-ZFP gene clusters encoding more than 100 of the approximately 360 mouse KRAB-ZFPs. We demonstrate that most KRAB-ZFPs bind to specific retrotransposon families and that many of these retrotransposons are transcriptionally activated in KRAB-ZFP cluster KO ESCs, licensing retrotransposon-derived enhancers to activate nearby genes. Overall design: RNA-seq analysis of KRAB-ZFP cluster KO ES cells and tissues.
Publication Title
KRAB-zinc finger protein gene expansion in response to active retrotransposons in the murine lineage.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples