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SRP092552
Mus musculus
86 Downloadable Samples
Illumina HiSeq 2000
Description
Huntington’s disease (HD) symptoms are driven to a large extent by dysfunction of the basal ganglia circuitry. HD patients exhibit reduced striatal phoshodiesterase 10 (PDE10) levels. Using HD mouse models that exhibit reduced PDE10, we demonstrate the benefit of pharmacologic PDE10 inhibition to acutely correct basal ganglia circuitry deficits. PDE10 inhibition restored corticostriatal input and boosted cortically driven indirect pathway activity. Cyclic nucleotide signaling is impaired in HD models and PDE10 loss may represent a homeostatic adaptation to maintain signaling. Elevation of both cAMP and cGMP by PDE10 inhibition were required for rescue. Phosphoproteomic profiling of striatum in response to PDE10 inhibition highlighted plausible neural substrates responsible for the improvement. Early chronic PDE10 inhibition in Q175 mice showed improvements beyond those seen with acute administration after symptom onset, including partial reversal of striatal deregulated transcripts and the prevention of the emergence of HD neurophysiological deficits. Overall design: Transcriptional profiling of cortex and striatal tissue following chronic dosing of either vehicle or the PDE10A inhibitor PF-02545920 (0.32, 1 and 3.2 mg/kg po qd) in the Q175 homozygous knock-in mouse model of Huntington’s disease (dosing from 5-weeks to 9 months of age).
Publication Title
Phosphodiesterase 10A Inhibition Improves Cortico-Basal Ganglia Function in Huntington's Disease Models.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 40 Downloadable Samples
- Illumina HiSeq 2000
Description
Genetically encoded unnatural amino acids provide powerful strategies for modulating the molecular functions of proteins in mammalian cells. However this approach has not been coupled to genome-wide measurements, because efficient unnatural amino acid incorporation is limited to readily transfectable cells and leads to very heterogeneous expression. We demonstrate that rapid piggybac integration of the orthogonal pyrrolysyl-tRNA synthetase (PylS)/tRNAPyl CUA pair (and its derivatives) into the mammalian genome enables efficient, homogeneous unnatural amino acid incorporation into target proteins in diverse cells, and we reveal the distinct transcriptional responses of ES cells and MEFs to amber suppression. Genetically encoding Ne-acetyl-lysine in place of six lysine residues in histone H3, that are known to be post-translationally acetylated, enables deposition of pre-acetylated histones into cellular chromatin, via a synthetic pathway that is orthogonal to enzymatic modification, allowing us to determine the consequences of acetylation at specific amino acids in histones on gene expression. Overall design: mRNA was sequenced using polyA-enrichment and Truseq library preparation protocol. Two biological replicates were sequences for each cell line and condition
Publication Title
Genetic code expansion in stable cell lines enables encoded chromatin modification.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Thyroid hormone has a positive effect on endochondral bone growth. Few studies have looked at the interaction between thyroid hormone exposures and intramembranous bone derived cells. We used microarray as one tool to determine the gene expression profile of intramembranous (calvarial) derived murine pre-osteoblsts after thyroxine exposure.
Publication Title
Effects of thyroxine exposure on osteogenesis in mouse calvarial pre-osteoblasts.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
Endogenous retroviruses (ERVs) have provided an evolutionary advantage in the diversification of transcript regulation and are thought to be involved in the establishment of extraembryonic tissues during development. However, silencing of these elements remains critical for the maintenance of genome stability. Here, we define a new chromatin state that is uniquely characterized by the combination of the histone variant H3.3 and H3K9me3, two chromatin ‘marks’ that have previously been considered to belong to fundamentally opposing chromatin states. H3.3/H3K9me3 heterochromatin is fundamentally distinct from ‘canonical’ H3K9me3 heterochromatin that has been under study for decades and this unique functional interplay of a histone variant and a repressive histone mark is crucial for silencing ERVs in ESCs. Our study solidifies the emerging notion that H3.3 is not a histone variant associated exclusively with “active” chromatin and further suggests that its incorporation at unique heterochromatic regions may be central to its function during development and the maintenance of genome stability. Overall design: RNA-seq analysis of three embryonic stem cell lines WT, H3.3 KO1, and H3.3 KO2)
Publication Title
Histone H3.3 is required for endogenous retroviral element silencing in embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Gene expression analysis under normal culture conditions (RPMI-10%FBS) and at optimal cell densities.
Publication Title
Low-risk susceptibility alleles in 40 human breast cancer cell lines.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
To address the role of INO80/SWR-type remodeling complexes, we deleted Ep400 at defined times of mouse oligodendrocyte development. Whereas oligodendrocyte precursors are specified and develop normally without Ep400, terminal differentiation is dramatically impaired resulting in hypomyelination. RNA-Seq studies were performed on cultured and FACS sorted control and Ep400-deficient mouse oligodendrocytes to analyze changes in gene expression. These revealed that genes associated with the myelination program and with response to DNA damage are altered in Ep400-deficient oligodendrocytes. Overall design: OPC mRNA profiles of 6-day old control (ctrl) and Ep400 cko mice were generated using the Illumina HiSeq 2500 platform.
Publication Title
Chromatin remodeler Ep400 ensures oligodendrocyte survival and is required for myelination in the vertebrate central nervous system.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This is to compare the gene expression profile of Th1 and Th17 cells.
Publication Title
Late developmental plasticity in the T helper 17 lineage.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The cortical area map is initially patterned by transcription factor (TF) gradients in the neocortical primordium, which define a protomap in the embryonic ventricular zone (VZ). However, mechanisms that propagate regional identity from VZ progenitors to cortical plate (CP) neurons are unknown. Here we show that the VZ, subventricular zone (SVZ), and CP contain distinct molecular maps of regional identity, reflecting different gene expression gradients in radial glia progenitors, intermediate progenitors, and projection neurons, respectively. The intermediate map in SVZ is modulated by Eomes (also known as Tbr2), a T-box TF. Eomes inactivation caused rostrocaudal shifts in SVZ and CP gene expression, with loss of corticospinal axons and gain of corticotectal projections. These findings suggest that cortical areas and connections are shaped by sequential maps of regional identity, propagated by the Pax6 Eomes Tbr1 TF cascade. In humans, PAX6, EOMES, and TBR1 have been linked to intellectual disability and autism.
Publication Title
The protomap is propagated to cortical plate neurons through an Eomes-dependent intermediate map.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Areas and layers of the cerebral cortex are specified by genetic programs that are initiated in progenitor cells and then, implemented in postmitotic neurons. Here, we report that Tbr1, a transcription factor expressed in postmitotic projection neurons, exerts positive and negative control over both regional (areal) and laminar identity. Tbr1 null mice exhibited profound defects of frontal cortex and layer 6 differentiation, as indicated by down-regulation of gene-expression markers such as Bcl6 and Cdh9. Conversely, genes that implement caudal cortex and layer 5 identity, such as Bhlhb5 and Fezf2, were up-regulated in Tbr1 mutants. Tbr1 implements frontal identity in part by direct promoter binding and activation of Auts2, a frontal cortex gene implicated in autism. Tbr1 regulates laminar identity in part by downstream activation or maintenance of Sox5, an important transcription factor controlling neuronal migration and corticofugal axon projections. Similar to Sox5 mutants, Tbr1 mutants exhibit ectopic axon projections to the hypothalamus and cerebral peduncle. Together, our findings show that Tbr1 coordinately regulates regional and laminar identity of postmitotic cortical neurons.
Publication Title
Tbr1 regulates regional and laminar identity of postmitotic neurons in developing neocortex.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 26 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To identify mechanisms behind immunosuppression during virus infections, we infected mice with LCMV-Armstrong and LCMV-Clone 13 expression patterns. LCMV-Armstrong induces a T-cell reaction that resolves infection within 8-10 days, while LCMV-Clone13 generates a persisten infection through immunosuppression.
Publication Title
Blockade of chronic type I interferon signaling to control persistent LCMV infection.
Sample Metadata Fields
Specimen part
View Samples