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Mus musculus
77 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
L-3,4-dihydroxyphenylalanine (levodopa) treatment is the major pharmacotherapy for Parkinson's disease. However, almost all patients receiving levodopa eventually develop debilitating involuntary movements (dyskinesia). While it is known that striatal spiny projection neurons (SPNs) are involved in the genesis of this movement disorder, the molecular basis of dyskinesia is not understood. In this study, we identify distinct cell-type-specific gene expression changes that occur in sub-classes of SPNs upon induction of a parkinsonian lesion followed by chronic levodopa treatment. We identify several hundred genes whose expression is correlated with levodopa dose, many of which are under the control of AP-1 and ERK signaling. In spite of homeostatic adaptations involving several signaling modulators, AP-1-dependent gene expression remains highly dysregulated in direct pathway SPNs (dSPNs) upon chronic levodopa treatment. We also discuss which molecular pathways are most likely to dampen abnormal dopaminoceptive signaling in spiny projection neurons, hence providing potential targets for antidyskinetic treatments in Parkinson's disease.
Publication Title
Molecular adaptations of striatal spiny projection neurons during levodopa-induced dyskinesia.
Sample Metadata Fields
Specimen part, Treatment
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SRP119989- Mus musculus
- 16 Downloadable Samples
Illumina HiSeq 2000
Description
Alterations to corticostriatal glutamatergic function are early pathophysiological changes associated with Huntington?s disease (HD). The factors that regulate the maintenance of corticostriatal glutamatergic synapses post-developmentally are not well understood. Recently, the striatum-enriched transcription factor Foxp2 was implicated in the development of these synapses. Here we show that, in mice, overexpression of Foxp2 in the adult striatum of two models of HD leads to rescue of HD-associated behaviors, while knockdown of Foxp2 in wild-type mice leads to development of HD-associated behaviors. We note that Foxp2 encodes the longest polyglutamine repeat protein in the human reference genome, and we show that it can be sequestered into aggregates with polyglutamine-expanded mutant Huntingtin protein (mHTT). Foxp2 overexpression in HD model mice leads to altered expression of several genes associated with synaptic function, genes which present new targets for normalization of corticostriatal dysfunction in HD. Overall design: 4 mice per group of each: Con+Con, Con+Foxp2, BACHD+Con, BACHD+Foxp2 Foxp2 or Control virus was injected into BACHD and Control mice, mRNA was isolated and sequenced
Publication Title
Control of Huntington's Disease-Associated Phenotypes by the Striatum-Enriched Transcription Factor Foxp2.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 70 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st), Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Global transcriptome profiling identifies KLF15 and SLC25A10 as modifiers of adipocytes insulin sensitivity in obese women.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
The aim of this study was to identify new genes controlling insulin sensitivity in adipocytes from obese women with either insulin-resistant (OIR) or -sensitive (OIS) adipocytes.
Publication Title
Global transcriptome profiling identifies KLF15 and SLC25A10 as modifiers of adipocytes insulin sensitivity in obese women.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st), Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
The aim of this study was to identify new genes controlling insulin sensitivity in adipocytes from obese women with either insulin-resistant (OIR) or -sensitive (OIS) adipocytes.
Publication Title
Global transcriptome profiling identifies KLF15 and SLC25A10 as modifiers of adipocytes insulin sensitivity in obese women.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 376 Downloadable Samples
- Illumina HiSeq 2500
Description
Ectopic expression of the transcription factors Oct4, Sox2, Klf4 and c-Myc (OSKM) can reprogram somatic cells into induced pluripotent stem cells (iPSCs). These iPSCs are highly similar to embryonic stem cells and can be used for regenerative medicine, drug screening and disease modelling. Despite recent advances, reprogramming is a slow and inefficient process. This suggests that there are several safeguarding mechanisms to counteract cell fate conversion. Cellular senescence is one of these barriers, which is mediated through activation of the tumour suppressors p53/p21CIP1, p15INK4b and p16INK4a. In this study, we have screened for shRNAs blunting reprogramming-induced senescence. We integrated single-cell RNA sequencing (scRNA-Seq) with shRNA screening to investigate the mechanism of action of the identified candidates. Overall design: 376 samples: 280 IMR90 cells expressing OSKM and shRNA library derived from the shRNA screen (bypassing senescence), 64 OSKM-expressing IMR90 cells (senescent), 32 IMR90 cells expressing control vector
Publication Title
Coupling shRNA screens with single-cell RNA-seq identifies a dual role for mTOR in reprogramming-induced senescence.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HiSeq 2000, Affymetrix Human Genome U219 Array (hgu219)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cell-Cycle-Dependent Reconfiguration of the DNA Methylome during Terminal Differentiation of Human B Cells into Plasma Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
Affymetrix Human Genome U219 Array (hgu219), Illumina HiSeq 2000
Description
Molecular mechanisms underlying terminal differentiation of B-cells into plasma cells are major determinants of adaptive immunity but remain only partially understood. Here, we present the transcriptional and epigenomic landscapes of cell subsets arising from activation of human naive B-cells and differentiation into plasmablasts. Cell proliferation of activated B cells was linked to a slight decrease in DNA methylation levels but followed by a committal step in which an S-phase-synchronized differentiation switch was associated with an extensive DNA demethylation and local acquisition of 5-hydroxymethylcytosine at enhancers and genes related to plasma cell identity.
Publication Title
Cell-Cycle-Dependent Reconfiguration of the DNA Methylome during Terminal Differentiation of Human B Cells into Plasma Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Nucleosome positioning changes during human embryonic stem cell differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Nucleosomes are the basic unit of chromatin. Nucleosome positioning (NP) plays a key role in transcriptional regulation and other biological processes. To better understand NP we used MNase-seq to investigate changes that occur as human embryonic stem cells (hESCs) transition to nascent mesoderm and then to smooth muscle cells (SMCs). Compared to differentiated cell derivatives, nucleosome occupancy at promoters and other notable genic sites, such as exon/intron junctions and adjacent regions, in hESCs shows a stronger correlation with transcript abundance and is less influenced by sequence content. Upon hESC differentiation, genes being silenced, but not genes being activated, display a substantial change in nucleosome occupancy at their promoters. Genome-wide, we detected a shift of NP to regions of higher G+C content as hESCs differentiate to SMCs. Notably, genomic regions with higher nucleosome occupancy harbor twice as many GC changes but fewer than half AT changes, compared to regions with lower nucleosome occupancy. Finally, our analysis indicates that the hESC genome is not rearranged and has a sequence mutation rate resembling normal human genomes. Our study reveals another unique feature of hESC chromatin, and sheds light on the relationship between nucleosome occupancy and sequence G+C content.
Publication Title
Nucleosome positioning changes during human embryonic stem cell differentiation.
Sample Metadata Fields
Specimen part, Cell line
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