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Homo sapiens
21 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Facioscapulohumeral muscular dystrophy (FSHD) represents a majorunmet clinical need arising from the progressive weakness and atrophy of skeletal muscles. The dearth of adequate experimental models has severely hampered our understanding of the disease. To date, no treatment is available for FSHD. Human embryonic stem cells (hESCs) potentially represent a renewable source of skeletal muscle cells (SkMCs) and provide an alternative to invasive patient biopsies.Wedeveloped a scalable monolayer system to differentiate hESCs into mature SkMCs within 26 days, without cell sorting or genetic manipulation. Here we show that SkMCs derived from FSHD1-affected hESC lines exclusively express the FSHD pathogenic marker double homeobox 4 and exhibit some of the defects reported in FSHD. FSHD1 myotubes are thinner when compared with unaffected and Becker muscular dystrophy myotubes, and differentially regulate genes involved in cell cycle control, oxidative stress response and cell adhesion. This cellularmodelwill be a powerful tool for studying FSHDandwill ultimately assist in the development of effective treatments for muscular dystrophies.
Publication Title
A Human Pluripotent Stem Cell Model of Facioscapulohumeral Muscular Dystrophy-Affected Skeletal Muscles.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 35 Downloadable Samples
Illumina HiSeq 2500
Description
The rising prevalence of obesity and its associated metabolic abnormalities have become global diseases that carry considerable morbidity and mortality. While there is certainly an important genetic component, extensive human epidemiologic and animal model data suggest an epigenetic component to obesity. Nevertheless, the cellular and molecular underpinnings of these pathways and how they contribute to the development of obesity remain to be elucidated. Suv420h1 and h2 are histone methyltransferases responsible for chromatin compaction and gene repression. Through in vivo, ex-vivo and in vitro studies, we found that Suv420h1 and h2 respond to environmental stimuli and regulate metabolism by downregulating PPAR-?, a master transcriptional regulator of lipid storage and glucose metabolism. Accordingly, mice lacking Suv420h proteins activate PPAR-? target genes in brown adipose tissue to increase mitochondria respiration, improve glucose tolerance and reduce adipose tissue to fight obesity. We conclude that Suv420h proteins are key epigenetic regulator of PPAR-? and the pathways controlling metabolism and weight balance in response to environmental stimuli. Overall design: For experiment 1, total RNA was isolated from males and females control- and Suv420h dKO-derived BAT. For experiment 2, total RNA was isolated from BAT collected from females control and Suv420h dKO mice after both diet regimes (nd = normal diet, hfd = high fat diet).
Publication Title
The Suv420h histone methyltransferases regulate PPAR-γ and energy expenditure in response to environmental stimuli.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples- Arabidopsis thaliana
- 81 Downloadable Samples
- Illumina HiSeq 4000
Description
The ability for cut tissues to join together and form a chimeric organism is a remarkable property of many plants, however, grafting is poorly characterized at the molecular level. To better understand this process we monitored genome-wide temporal and spatial gene expression changes in grafted Arabidopsis thaliana hypocotyls. Tissues above and below the graft rapidly developed an asymmetry such that many genes were more highly expressed on one side than the other. This asymmetry correlated with sugar responsive genes and we observed an accumulation of starch above the graft that decreased along with asymmetry once the sugar-transporting vascular tissues reconnected. Despite the initial starvation response below the graft, many genes associated with vascular formation were rapidly activated in grafted tissues but not in cut and separated tissues indicating that a recognition mechanism activated that was independent of functional vascular connections. Auxin which is transported cell-to-cell, had a rapidly elevated response that was symmetric, suggesting that auxin was perceived by the root within hours of tissue attachment to activate the vascular regeneration process. A subset of genes were expressed only in grafted tissues, indicating that wound healing proceeded via different mechanisms depending on the presence or absence of adjoining tissues. Such a recognition process could have broader relevance for tissue regeneration, inter-tissue communication and tissue fusion events. Overall design: We analyzed the poly-adenylated transcriptomes of Arabidopsis thaliana hypocotyle tissue during grafting. Our dataset contains 82 strand-specific samples, whereas each condition is represented by two biological replicates.
Publication Title
Transcriptome dynamics at <i>Arabidopsis</i> graft junctions reveal an intertissue recognition mechanism that activates vascular regeneration.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To identify the activity-induced gene expression programs in inhibitory and excitatory neurons, we analyzed RNA extracted from cultured E14 mouse MGE- and CTX-derived neurons (DIV 10) after these cultures were membrane-depolarized for 0, 1 and 6 hrs with 55mM extracellular KCl. To identify the gene programs regulated in these cells by the activity-induced early-response transcription factor Npas4, we repeated the same experiment in the MGE- and CTX-cultures lacking Npas4 (Npas4-KO).
Publication Title
Npas4 regulates excitatory-inhibitory balance within neural circuits through cell-type-specific gene programs.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Caenorhabditis elegans
- 7 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Six DD class GABAergic neurons are generated in the embryo to synapse with ventral muscles and receive input from cholinergic neurons in the dorsal nerve cord. After hatching and toward the end of the first larval (L1) stage, DD neurons reverse polarity (i.e., synapse with dorsal muscles, receive ventral cholinergic inputs). Expression profiles were generated from DD neurons in the early L1 stage before the initiation of the remodeling program.
Publication Title
Transcriptional Control of Synaptic Remodeling through Regulated Expression of an Immunoglobulin Superfamily Protein.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Brain inflammation, a common feature in neurodegenerative diseases, is a complex series of events, which can be detrimental and even lead to neuronal death. Nonetheless, several studies suggest that inflammatory signals are also positively influencing neural cell proliferation, survival, migration and differentiation. Recently, correlative studies suggested that astrocytes are able to dedifferentiate upon injury, and may thereby re-acquire neural stem cells (NSC) potential. However, the mechanism underlying this dedifferentiation process upon injury remains unclear. In this study, we find that during the early response of reactive gliosis, inflammation induces a conversion of mature astrocytes into neural progenitors. A TNF treatment induces the decrease of specific astrocyte markers, such as GFAP or genes related to glycogen metabolism, while a subset of these cells re-express immaturity markers, such as CD44, Musashi-1 and Oct4. Thus, TNF treatment results in the appearance of cells that exhibit a neural progenitor phenotype and are able to proliferate and differentiate into neurons and/or astrocytes.
Publication Title
Inflammation Promotes a Conversion of Astrocytes into Neural Progenitor Cells via NF-κB Activation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Disruption of the MECP2 gene leads to Rett syndrome (RTT), a severe neurological disorder with features of autism. MECP2 encodes a methyl-DNA-binding protein that is proposed to function as a transcriptional repressor, but, despite numerous studies examining neuronal gene expression in MeCP2 mutants, no coherent model has emerged for how MeCP2 regulates transcription. Here we identify a genome-wide length-dependent increase in the expression of long genes in neurons lacking MeCP2. This gene misregulation occurs in human RTT brains and correlates with onset and severity of phenotypes in Mecp2 mutant mice, suggesting that the disruption of long gene expression contributes to RTT pathology. We present evidence that MeCP2 represses long genes by binding to brain-enriched, methylated CA dinucleotides within genes and show that loss of methylated CA in the brain recapitulates gene expression defects observed in MeCP2 mutants. We find that long genes encode proteins with neuronal functions, and overlap substantially with genes that have been implicated in autism and Fragile X syndrome. Reversing the overexpression of long genes in neurons lacking MeCP2 can improve some RTT-associated cellular deficits. These findings suggest that a function of MeCP2 in the mammalian brain is to temper the expression of genes in a length-dependent manner, and that mutations in MeCP2 and possibly other autism genes may cause neurological dysfunction by disrupting the expression of long genes in the brain. Overall design: Total RNA-seq Data from the visual cortex of wild-type and MeCP2 knockout animals at 8-10 weeks of age
Publication Title
Disruption of DNA-methylation-dependent long gene repression in Rett syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 5 Downloadable Samples
- Illumina Genome Analyzer II
Description
Argonaute-associated siRNAs and Piwi-associated piRNAs have overlapping roles in silencing mobile genetic elements in animals. In C. elegans, mutator-class (mut) genes mediate siRNA-guided repression of transposons as well as exogenous RNA-directed gene silencing (RNAi), but their roles in endogenous RNA silencing pathways are not well understood. To characterize the endogenous small RNAs dependent on mutator-class genes, small RNA populations from a null allele of mut-16, as well as a regulatory mut-16(mg461) allele that disables only somatic RNAi, were subjected to deep sequencing. Overall design: Small RNA analysis in wild type and mut-16 mutant C. elegans strains
Publication Title
mut-16 and other mutator class genes modulate 22G and 26G siRNA pathways in Caenorhabditis elegans.
Sample Metadata Fields
Cell line, Subject
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GSE23028- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To identify differences in gene expression between peptidylprolyl isomerase F (cyclophilin D; Ppif)-null hearts and WT control hearts.
Publication Title
Cyclophilin D controls mitochondrial pore-dependent Ca(2+) exchange, metabolic flexibility, and propensity for heart failure in mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 4000
Description
We screened intronic microRNAs dysregulated in liver of obese mouse models to identify previously uncharacterized coding host genes that may contribute to the pathogenesis of obesity-associated insulin resistance and type 2 diabetes mellitus. Our approach identified the expression of Ectodysplasin A (Eda), the causal gene of X-linked hypohidrotic ectodermal dysplasia (XLHED; MIM 305100) was strongly increased in liver of obese mouse models both in rodents and humans.Eda expression in murine liver is controlled via PPAR? activation, increases in circulation and promotes JNK activation and inhibitory serine phosphorylation of IRS1 in skeletal muscle. Consistently, bi-directional modulation of hepatic Eda expression in mouse models affects systemic glucose metabolism with alterations of muscle insulin signaling, revealing a novel role of EDA as an obesity-associated hepatokine, which impairs insulin sensitivity in skeletal muscle. Overall design: Soleus muscle mRNA profiles of db/db mice at 3 weeks after injection of AAV encoding shRNA targeting mouse Eda or the control scrambled shRNA sequence at the titer of 2-3x10e10 particles/body.
Publication Title
A microRNA screen reveals that elevated hepatic ectodysplasin A expression contributes to obesity-induced insulin resistance in skeletal muscle.
Sample Metadata Fields
Age, Specimen part, Subject
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