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SRP059609
Mus musculus
20 Downloadable Samples
NextSeq 500, Illumina HiSeq 2000
Description
The KDM6 histone demethylases (UTX/KDM6A and JMJD3/KDM6B) mediate removal of repressive histone H3K27me3 marks to establish transcriptionally permissive chromatin. Loss of UTX in female mice is embryonic lethal. Unexpectedly, male UTX-null mice escape embryonic lethality due to expression of UTY, a paralog lacking H3K27-demethylase activity. This suggests that UTX plays an enzyme-independent role in development, and challenges the need for active H3K27-demethylation in vivo. However, the requirement for active H3K27-demethylation in stem cell-mediated tissue regeneration remains untested. Using an inducible mouse knockout that ablates UTX in satellite cells, we show that active H3K27-demethylation is necessary for muscle regeneration. Indeed, loss of UTX in satellite cells blocks myofiber regeneration in both male and female mice. Furthermore, we demonstrate that UTX mediates muscle regeneration through its H3K27-demethylase activity using a chemical inhibitor, and a demethylase-dead UTX knock-in mouse. Mechanistically, dissection of the muscle regenerative process revealed that UTX is required for expression of the transcription factor Myogenin that drives differentiation of muscle progenitors. Thus, we have identified a critical role for the enzymatic activity of UTX in activating muscle-specific gene expression during myofiber regeneration, revealing for the first time that active H3K27-demethylation has a physiological role in vivo. Overall design: Satellite cells were sorted based on Cre-dependent expression of TdT reporter gene. Sorted UTXmKO or UTX WT satellite cells were then induced to differentiate for 24 hrs. RNA was then isolated and subjected to RNA-Seq analysis.
Publication Title
UTX demethylase activity is required for satellite cell-mediated muscle regeneration.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mitogen activated protein kinase (MAPK) signaling regulates differentiation of many cell types. During myogenesis in particular, p38a MAPK (MAPK14) phosphorylates multiple transcriptional regulators to modulate muscle-specific gene expression. Among the p38a MAPK modulated genes is the muscle-specific transcriptional regulator Myogenin (Myog) that is also essential to complete the muscle differentiation program, and while it is known that both p38a MAPK and Myog are critically required for myogenesis, the individual contribution of each of these proteins is poorly defined. Here we show that Myog expression (in the absence of p38a MAPK signaling) is sufficient to establish expression of many late markers of muscle differentiation and to mediate cell migration. However, Myog expression alone did not led to the formation of multinucleated muscle cells, highlighting a critical role for p38a MAPK in myoblast fusion. Using comparative microarray analysis we identified p38a MAPK-dependent genes that are not regulated by Myog
Publication Title
Comparative expression profiling identifies differential roles for Myogenin and p38α MAPK signaling in myogenesis.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Trichostatin A enhances vascular repair by injected human endothelial progenitors through increasing the expression of TAL1-dependent genes.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Endothelial colony-forming cells (ECFCs) have been reported as promising cells for regenerative medicine thanks to their angiorepair properties. Transcription factors are primary determinants of the functional capacity of the cells and TAL1 has been shown as a critical regulator of endothelial lineage in both development and adult life. However, only few (three) TAL1 targets have been identified so far in mouse and human endothelial cells. This microarray experiment, where TAL1 expression was knocked-down, was designed to identify TAL1-dependent genes in primary human endothelial stem/progenitor cells.
Publication Title
Trichostatin A enhances vascular repair by injected human endothelial progenitors through increasing the expression of TAL1-dependent genes.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Muscle denervation due to injury, disease or aging results in impaired motor function. Restoring neuromuscular communication requires axonal regrowth and regeneration of neuromuscular synapses. Muscle activity inhibits neuromuscular synapse regeneration. The mechanism by which muscle activity regulates regeneration of synapses is poorly understood. Dach2 and Hdac9 are activity-regulated transcriptional co-repressors that are highly expressed in innervated muscle and suppressed following muscle denervation. Here, we report that Dach2 and Hdac9 inhibit regeneration of neuromuscular synapses. Importantly, we identified Myog and Gdf5 as muscle-specific Dach2/Hdac9-regulated genes that stimulate neuromuscular regeneration in denervated muscle. Interestingly, Gdf5 also stimulates presynaptic differentiation and inhibits branching of regenerating neurons. Finally, we found that Dach2 and Hdac9 suppress miR206 expression, a microRNA involved in enhancing neuromuscular regeneration. Overall design: RNAseq on innervated and 3 day denervated adult soleus muscle from wildtype mice is compared with that from 3 day denervated soleus muscle from Dach2/Hdac9 deleted mice to identify Dach2/Hdac9-regulated genes.
Publication Title
Dach2-Hdac9 signaling regulates reinnervation of muscle endplates.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hypercholesterolemic APOE-deficient mice are a widely used experimental model of atherosclerosis and increased generation of reactive oxygen species (ROS) is a prominent feature of atherosclerosis development. To study the impact of ROS on atherogenesis, we treated APOE-deficient mice for 7 months with the antioxidant vitamin E (2000 IU/kg diet) and performed whole genome microarray gene expression profiling of aortic genes. Microarray gene expression profiling was performed of whole aortas isolated from vitamin E-treated APOE-deficient relative to untreated APOE-deficient mice with overt atherosclerosis, and nontransgenic B6 control mice. Microarray gene expression profiling revealed that vitamin E treatment prevented atherosclerosis-related gene expression changes of the aortic intima and media.
Publication Title
Microarray gene expression profiling reveals antioxidant-like effects of angiotensin II inhibition in atherosclerosis.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
miRNA sequencing of mammary tumor RNA from 18 [AKXD subline(n) x PyMT]F1. The PyMT strain was FVB/N-TgN(MMTV-PyVT)634Mul. Overall design: Mammary tumor total small RNA from mice representing each of the 18 AKXD RI strains was pooled to represent each strain and sequenced using the Illumina Genome Analyzer IIx sequencer.
Publication Title
An integrated systems genetics screen reveals the transcriptional structure of inherited predisposition to metastatic disease.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
ADHD is the most common neurobehavioral disorder in school-aged children. In addition to genetic factors, environmental influences or gene x environmental interactions also play an important role in ADHD. One example of a well studied environmental risk factor for ADHD is exposure to polychlorinated biphenyls (PCBs). In this study, we investigated whether the well-established genetic model of ADHD based on the Spontaneously Hypertensive Rat (SHR) and a well established PCB-based model of ADHD exhibited similar molecular changes in brain circuits involved in ADHD. The brains from 28 male rats (8 SHR, 8 Sprague-Dawley (SD) controls, 8 Wistar-Kyoto (WKY) controls, and 4 PCB-exposed SD rats) were harvested at postnatal day 55-65 and RNA was isolated from six brain regions of interest. The RNA was analyzed for differences in expression of a set of 308 probe sets interrogating 218 unique genes considered highly relevant to ADHD or epigenetic gene regulation using the Rat RAE 230 2.0 GeneChip (Affymetrix). Selected observations were confirmed by real time quantitative RT-PCR. The results show that the expression levels of genes Gnal, COMT, Adrbk1, Ntrk2, Hk1, Syt11 and Csnk1a1 were altered in both the SHR rats and the PCB-exposed SD rats. Arrb2, Stx12, Aqp6, Syt1, Ddc and Pgk1 expression levels were changed only in the PCB-exposed SD rats. Genes with altered expression only in the SHRs included Oprm1, Calcyon, Calmodulin, Lhx1 and Hes6.The epigenetic genes Crebbp, Mecp2 and Hdac5 are significantly altered in both models. The data provide strong evidence that genes and environment can affect different set of genes in two different models of ADHD and yet result in the similar disease-like symptoms.
Publication Title
A comparison of molecular alterations in environmental and genetic rat models of ADHD: a pilot study.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Ligand-mediated activation of the nuclear hormone receptor PPAR gamma lowers blood pressure and improves glucose tolerance in humans. Two naturally occurring mutations (P467L, V290M) in the ligand binding domain of PPAR gamma have been described in humans that lead to severe insulin resistance and hypertension. Experimental evidence suggests that these mutant versions of PPAR gamma act in a dominant negative fashion. To better understand the molecular mechanisms underlying PPAR gamma action in the vasculature, we determined the global gene expression profile in primary aortic endothelial cells in response to endothelial cell specific expression of a dominant negative isoform of PPAR gamma (V290M).
Publication Title
Endothelium-specific interference with peroxisome proliferator activated receptor gamma causes cerebral vascular dysfunction in response to a high-fat diet.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2000
Description
The heat shock response (HSR) is a mechanism to cope with proteotoxic stress by inducing the expression of molecular chaperones and other heat shock response genes. The HSR is evolutionarily well conserved and has been widely studied in bacteria, cell lines and lower eukaryotic model organisms. However, mechanistic insights into the HSR in higher eukaryotes, in particular in mammals, are limited. We have developed an in vivo heat shock protocol to analyze the HSR in mice and dissected heat shock factor 1 (HSF1)-dependent and -independent pathways. Whilst the induction of proteostasis-related genes was dependent on HSF1, the regulation of circadian function related genes, indicating that the circadian clock oscillators have been reset, was independent of its presence. Furthermore, we demonstrate that the in vivo HSR is impaired in mouse models of Huntington's disease but we were unable to corroborate the general repression of transcription after a heat shock found in lower eukaryotes. Overall design: RNA-Seq was performed on mRNA isolated from quadriceps femoris muscle of 24 mice. These mice were of wild type, R6/2, and Hsf1-/- genotypes. Two mice of each genotype were tested in four conditions: (1) heat shock, (2) control heat shock, (3) HSP90 inhibition (NVP-HSP990), and (4) HSP90 inhibition vehicle.
Publication Title
HSF1-dependent and -independent regulation of the mammalian in vivo heat shock response and its impairment in Huntington's disease mouse models.
Sample Metadata Fields
Age, Specimen part, Treatment, Subject
View Samples