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SRP119123
Mus musculus
36 Downloadable Samples
Illumina HiSeq 2000
Description
Alzheimer's disease is a devastating neurodegenerative disease eventually leading to dementia. An effective treatment does not yet exist. Here we show that oral application of the compound anle138b restores hippocampal synaptic and transcriptional plasticity as well as spatial memory in a mouse model for Alzheimer's disease, when given orally before or after the onset of pathology. At the mechanistic level we provide evidence that anle138b blocks the formation of conducting Aß pores without changing the membrane embedded Aß-oligomer structure. In conclusion, our data suggest that anle138b is a novel and promising compound to treat AD-related pathology that should be investigated further. Overall design: APPdelta9 and Wildtype mouse treated with anle138b or placebo
Publication Title
The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology.
Sample Metadata Fields
Age, Cell line, Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
RNA-Seq and expression microarray highlight different aspects of the fetal amniotic fluid transcriptome.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The second trimester fetal transcriptome can be assessed based on cell-free RNA found within the amniotic fluid supernatant. The objective of this study was to compare the suitability of two technologies for profiling the human fetal transcriptome: RNA-Seq and expression microarray. Comparisons were based on total numbers of gene detected, rank-order gene expression, and functional genomic analysis.
Publication Title
RNA-Seq and expression microarray highlight different aspects of the fetal amniotic fluid transcriptome.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Monoallelic expression of autosomal genes (MAE) is a widespread epigenetic phenomenon which is poorly understood, due in part to current limitations of genome-wide approaches for assessing it. Recently, we reported that a specific histone modification signature is strongly associated with MAE, and demonstrated that it can serve as a proxy of MAE in human lymphoblastoid cells (Nag et al. Elife. 2013 Dec 31;2:e01256). Here, we use murine cells to establish that this chromatin signature is conserved between mouse and human, and is associated with MAE in every tested cell type. Our analyses reveal extensive conservation in the identity of MAE genes between the two species. By applying MAE chromatin signature analysis to a large number of cell and tissue types, we show that the MAE state remains consistent during terminal cell differentiation and is predominant among cell-type specific genes, suggesting a link between MAE and specification of cell identity. Overall design: PolyA RNA purification and subsequent high-throughput sequencing were performed on two independent B-lymphoid clonal cell line, derived from 129S1/SvImJ x CAST/EiJ F1 mice and immortalized with Abelson murine leukemia virus, and on two independent fibroblast clonal cell lines, derived from 129S1/Sv x CAST/EiJ F1 and immortalized with SV40.
Publication Title
Chromatin Signature Identifies Monoallelic Gene Expression Across Mammalian Cell Types.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 199 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Notch signaling plays both oncogenic and tumor suppressor roles, depending on cell type. In contrast to T cell acute lymphoblastic leukemia (T-ALL), where Notch activation promotes leukemogenesis, induction of Notch signaling in B-ALL leads to growth arrest and apoptosis. The Notch target Hairy/Enhancer of Split1 (HES1) is sufficient to reproduce this tumor suppressor phenotype in B-ALL, however the mechanism is not yet known. Here we report that HES1 regulates pro-apoptotic signals via the novel interacting protein Poly ADP-Ribose Polymerase1 (PARP1) in a cell type-specific manner. The interaction of HES1 with PARP1 inhibits HES1 function, induces PARP1 activation and results in PARP1 cleavage in B-ALL. HES1-induced PARP1 activation leads to self-ADP ribosylation of PARP1, consumption of NAD+, diminished ATP levels, and translocation of the Apoptosis Inducing Factor (AIF) from mitochondria to the nucleus, resulting in apoptosis in B-ALL, but not T-ALL. Importantly, induction of Notch signaling via the Notch agonist peptide DSL can reproduce these events and leads to BALL apoptosis. The novel interaction of HES1 and PARP1 in B-ALL modulates the function of the HES1 transcriptional complex and signals through PARP1 to induce apoptosis. This mechanism reveals a cell type-specific pro-apoptotic pathway which may lead to Notch agonist-based cancer therapeutics.
Publication Title
Notch/HES1-mediated PARP1 activation: a cell type-specific mechanism for tumor suppression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Throughout postnatal life in mammals, neural stem cells (NSCs) are located in the subventricular zone (SVZ) of the lateral ventricles. The greatest diversity of neuronal and glial lineages they generate occurs during early postnatal life in a region-specific manner. In order to evaluate potential heterogeneity in the NSC pool, we microdissected the dorsal and lateral SVZ at different postnatal ages and isolated NSCs and their immediate progeny based on their expression of Hes5-EGFP/Prominin1 and Ascl1-EGFP, respectively. Whole genome comparative transcriptome analysis revealed transcriptional regulators as major hallmarks that sustain postnatal SVZ regionalization. Manipulation of single genes encoding for locally enriched transcription factors influenced NSC specification indicating that the fate of regionalized postnatal SVZ NSCs can be readily modified . These findings reveal functional heterogeneity of NSCs in the postnatal SVZ and provide targets to recruit region-specific lineages in regenerative contexts.
Publication Title
Transcriptional Hallmarks of Heterogeneous Neural Stem Cell Niches of the Subventricular Zone.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Expression of mutant lamins in human muscle causes muscular dystrophy. We have generated a drosophila model that expresses mutant lamins, modeled after those that cause disease in humans.
Publication Title
Myopathic lamin mutations cause reductive stress and activate the nrf2/keap-1 pathway.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
The purpose of this study was to characterise the effects of trastuzumab and pertuzumab, either as single agents or as combination therapy on gene and protein expression in human ovarian cancer in vivo. Illumina BeadChips were used to profile the transcriptome after four days treatment of SKOV3 tumor xenografts. Although genes involved with HER2, MAP-kinase and p53 signaling pathways were commonly induced by all treatments, a greater number and variety of genes were differentially expressed by the complementary combination therapies compared to either drug on its own. The protein level of the CDK-inhibitors p21 and p27 were increased in response to both agents alone and further by the combination; pERK signaling was inhibited by all treatments; but only pertuzumab alone inhibited pAkt signaling. The expression of proliferation, apoptosis, cell division and cell cycle markers was distinct in a panel of primary ovarian cancer xenografts, suggesting heterogeneity of response in ovarian cancer and the need to establish biomarkers of response.
Publication Title
Defining the molecular response to trastuzumab, pertuzumab and combination therapy in ovarian cancer.
Sample Metadata Fields
Cell line
View Samples- Arabidopsis thaliana
- 21 Downloadable Samples
Arabidopsis Gene 1.1 ST Array (aragene11st), Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The Small Molecule Hyperphyllin Enhances Leaf Formation Rate and Mimics Shoot Meristem Integrity Defects Associated with AMP1 Deficiency.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Arabidopsis Gene 1.1 ST Array (aragene11st)
Description
ALTERED MERISTEM PROGRAM1 (AMP1) is a member of the M28 family of carboxypeptidases with a pivotal role in plant development and stress adaptation. Its most prominent mutant defect is a unique hypertrophic shoot phenotype combining a strongly increased organ formation rate with enhanced meristem size and the formation of ectopic meristem poles. However, so far the role of AMP1 in shoot development could not be assigned to a specific molecular pathway nor is its biochemical function resolved. We used a chemical genetic approach to identify the drug hyperphyllin (HP), which specifically mimics the shoot defects of amp1, including plastochron reduction and enlargement and multiplication of the shoot meristem. To further assess whether hyperphyllin acts in an AMP1-dependent manner we compared the transcriptonal responses of hyperphyllin-treated wild-type and amp1 mutant seedlings.
Publication Title
The Small Molecule Hyperphyllin Enhances Leaf Formation Rate and Mimics Shoot Meristem Integrity Defects Associated with AMP1 Deficiency.
Sample Metadata Fields
Specimen part, Treatment
View Samples