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GSE99890
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Impact of mmu-miR-337-3p on the global gene expression in murine hepatoblasts.
Publication Title
MicroRNA-337-3p controls hepatobiliary gene expression and transcriptional dynamics during hepatic cell differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
IlluminaHiSeq2000
Description
The rising incidence of obesity and related disorders such as diabetes and heart disease has focused considerable attention on the discovery of novel therapeutics. One promising approach has been to increase the number or activity of brown-like adipocytes in white adipose depots, as this has been shown to prevent diet-induced obesity and reduce the incidence and severity of type 2 diabetes. Thus, the conversion of fat-storing cells into metabolically active thermogenic cells has become an appealing therapeutic strategy to combat obesity. Here, we report a screening platform for the identification of small molecules capable of promoting a white-to-brown metabolic conversion in human adipocytes. We identified two inhibitors of Janus Kinase (JAK) activity with no precedent in adipose tissue biology that permanently confer brown-like metabolic activity to white adipocytes. Importantly, these metabolically converted adipocytes exhibit elevated UCP1 expression and increased mitochondrial activity. We further found that repression of interferon signalling and activation of hedgehog signalling in JAK-inactivated adipocytes contributes to the metabolic conversion observed in these cells. Our findings highlight a novel role for the JAK/STAT pathway in the control of adipocyte function and establish a platform to identify compounds for the treatment of obesity. Overall design: Human pluripotent stem-cell derived mesenchymal progenitor cells (PSC-MPCs), white adipose cells (PSC-WA), and brown adipose cells (PSC-BA) were treated with DMSO (as control), a JAK3-inhibitor compound, and a SYK-inhibitor compound respectively. Transcriptomic expression profiling was performed at 24 hours and 7 days respectively. Three biological replicates are available for each condition defined by cell type, compound, and time.
Publication Title
White-to-brown metabolic conversion of human adipocytes by JAK inhibition.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 36 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Bromodomain-dependent stage-specific male genome programming by Brdt.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 36 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Male germ cell differentiation is a highly regulated multistep process initiated by the commitment of progenitor cells into meiosis and characterized by major chromatin reorganizations in haploid spermatids. We report here that a single member of the double bromodomain BET factors, Brdt, is a master regulator of both meiotic divisions and post-meiotic genome repackaging. Upon its activation at the onset of meiosis, Brdt drives and determines the developmental timing of a testis-specific gene expression program. In meiotic cells, Brdt initiates a genuine histone acetylation-guided programming of the genome by activating essential meiotic genes and repressing a progenitor cells gene expression program, while priming a post-meiotic gene group for further activation. At post-meiotic stages, a global chromatin hyperacetylation gives the signal for Brdts first bromodomain to direct the genome-wide replacement of histones by transition proteins. Brdt is therefore a unique and essential regulator of male germ cell differentiation, which, by using various domains in a developmentally controlled manner, first drives a specific spermatogenic gene expression program, and later controls the tight packaging of the male genome.
Publication Title
Bromodomain-dependent stage-specific male genome programming by Brdt.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Neuropathic pain is an apparently spontaneous experience triggered by abnormal physiology of the peripheral or central nervous system, which evolves with time. Neuropathic pain arising from peripheral nerve injury is characterized by a combination of spontaneous pain, hyperalgesia and allodynia. There is no evidence of this type of pain in human infants or rat pups; brachial plexus avulsion, which causes intense neuropathic pain in adults, is not painful when the injury is sustained at birth. Since infants are capable of nociception from before birth and display both acute and chronic inflammatory pain behaviour from an early neonatal age, it appears that the mechanisms underlying neuropathic pain are differentially regulated over a prolonged postnatal period.
Publication Title
Differential regulation of immune responses and macrophage/neuron interactions in the dorsal root ganglion in young and adult rats following nerve injury.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide nucleosome specificity and function of chromatin remodellers in ES cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Analysis of human iPS-derived cardiomyocytes exposed to glucose, endothelin-1 and cortisol in vitro. Treatment produces a surrogate diabetic cardiomyopathic phenotype. Results provide insight into the pathways regulated by the treatment in the cardiomyocyte.
Publication Title
Disease modeling and phenotypic drug screening for diabetic cardiomyopathy using human induced pluripotent stem cells.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 1000
Description
Although the conserved AAA ATPase – bromodomain factor, ATAD2, has been described as a transcriptional co-activator upregulated in many cancers, its function remains poorly understood. Here, using a combination of ChIP-seq, ChIP-proteomics and RNA-seq experiments in embryonic stem cells, we found that Atad2 is an abundant nucleosome-bound protein present on active genes, associated with chromatin remodelling, DNA replication and DNA repair factors. A structural analysis of its bromodomain and subsequent investigations demonstrate that histone acetylation guides ATAD2 to chromatin, resulting in an overall increase of chromatin accessibility and histone dynamics, which is required for the proper activity of the highly expressed gene fraction of the genome. While in exponentially growing cells Atad2 appears dispensable for cell growth, in differentiating ES cells, Atad2 becomes critical in sustaining specific gene expression programs, controlling proliferation and differentiation. Altogether, this work defines Atad2’s function as a facilitator of general chromatin-templated activities such as transcription. Overall design: We used a siRNA approach to knock-down Atad2 and measure the resulting variations in gene expression by RNA-seq
Publication Title
Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
How various ATP-dependent chromatin remodellers bind to nucleosomes to regulate transcription is not well defined in mammalian cells. Here, we present genome-wide remodeller-interacting nucleosome profiles for Chd1, Chd2, Chd4, Chd6, Chd8, Chd9, Brg1 and Ep400 in mouse embryonic stem (ES) cells. These remodellers bind to nucleosomes at specific positions, either at one or both nucleosomes that flank each side of nucleosome-free promoter regions (NFRs), at enhancer elements, or within gene bodies. At promoters, bidirectional transcription commonly initiates on either side of remodeller-bound nucleosomes. Transcriptome analysis upon remodeller depletion reveals reciprocal mechanisms of transcriptional regulation by remodellers. At active genes, certain remodellers are positive regulators of transcription, whereas others act as repressors. At bivalent genes, which are bound by repressive Polycomb complexes, the same remodellers act in the opposite way. Together, these findings reveal how remodellers integrate promoter nucleosomal architecture to regulate ES cell transcription programs.
Publication Title
Genome-wide nucleosome specificity and function of chromatin remodellers in ES cells.
Sample Metadata Fields
No sample metadata fields
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