Skeletal muscle is a highly adaptable tissue capable of changes in size, contractility, and metabolism according to functional demands. Atrophy is a decline in mass and strength caused by pathologic loss of myofibrillar proteins, and can result from disuse, aging, or denervation caused by injury or peripheral nerve disorders. We provide a high-quality longitudinal RNA-Seq dataset of skeletal muscle from a cohort of adult C57BL/6J male mice subjected to tibial nerve denervation for 0 (baseline), 1, 3, 7, 14, 30, or 90 days. Using an unbiased genomics approach to identify gene expression changes across the entire longitudinal course of muscle atrophy affords the opportunity to 1) establish acute responses to denervation, 2) detect pathways that mediate rapid loss of muscle mass within the first week after denervation, and 3) capture the molecular phenotype of chronically atrophied muscle at a stage when it is largely resistant to recovery.
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Sex, Age, Specimen part, Disease, Cell line, Treatment
View SamplesE47 is a basic Helix Loop Helix (bHLH) transcription factor that has important roles in cell fate determination and differentiation of many cell types. In the nervous system E47 heterodimerizes with tissue-specific, pro-neural bHLH transcription factors and activates downstream target genes. To identify the relevant target genes of bHLH transcription factors in neural cells, we performed gene expression profiling of the human neuroblastoma cell line SK-N-SH engineered to acutely express ectopic E47 by an adenoviral vector. The experiments were done at two time points following adenoviral infection, 8 hours and 20 hours. Genes induced by E47 after 8 hours are likely to be direct targets of this transcription factor.
Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and axonal growth.
Specimen part, Cell line, Time
View SamplesAlthough the master transcription factors are the key to the development of specific T cell subsets, whether additional transcriptional regulators are induced by the same stimuli that dominantly repress development of other T cell lineages have not been fully elucidated. Using Transforming growth factor-ß (TGF-ß) induced iTreg system, we set out to identify transcriptional regulators that would work together with Foxp3 but at the same time repress other T cell subsets to ensure unopposed development of iTregs. Here we show that Musculin (MSC, or ABF-1), a basic helix-loop-helix (bHLH) transcription factor, which is induced by Smad3 under TGF-ß stimulation, is not only critical for iTreg cell development but promotes development of iTregs by repressing the Th2 transcriptional program. Loss of MSC reduces Foxp3 expression and induces Th2 differentiation even under TGF-ß induced iTreg differentiation conditions. MSC mediates this effect by physically interacting with GATA3, by interrupting binding of GATA3 to the Th2 cytokine locus and by reducing intrachromosomal interactions within the Th2 cytokine gene cluster. iTregs from MSC-deficient mice are not able to suppress Th2 responses and the Msc–/– mice spontaneously develop gut and lung inflammation with age. Our data indicate that MSC enforces Foxp3 expression and promotes unidirectional induction of iTregs by repressing development of the Th2 developmental program.
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Sex, Age, Specimen part, Cell line
View SamplesWe compared gene expression profiles between asymptomatic and symptomatic atherosclerotic plaques from the same patient. This was accomplished by analyzing carotid plaques from four patients with bilateral high-grade carotid artery stenoses one being symptomatic (TIA or stroke) and the other asymptomatic.
Microarray analysis reveals overexpression of CD163 and HO-1 in symptomatic carotid plaques.
Sex, Age, Specimen part, Disease, Disease stage, Subject, Time
View SamplesTo investigate the transcriptome changes of neuron and astrocyte post heat stress.
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View SamplesThis data set was generated by the UK Brain Expression Consortium and consists of gene expression data generated from post-mortem human brain samples, dissected from 10 brain regions and originating from a large cohort of neurologically and neuropathologically normal individuals.
Analysis of gene expression data using a linear mixed model/finite mixture model approach: application to regional differences in the human brain.
Sex, Disease, Subject
View SamplesThis data set was generated by the UK Brain Expression Consortium and consists of gene expression data generated from post-mortem human brain samples, dissected from 10 brain regions and originating from a large cohort of neurologically and neuropathologically normal individuals.
Widespread sex differences in gene expression and splicing in the adult human brain.
Sex, Disease, Subject
View SamplesThis data set was generated by the UK Brain Expression Consortium and consists of gene expression data generated from post-mortem human brain samples, dissected from 10 brain regions and originating from a large cohort of neurologically and neuropathologically normal individuals.
Widespread sex differences in gene expression and splicing in the adult human brain.
Sex, Disease, Subject
View SamplesDirected differentiation of midbrain dopaminergic neurons from human embryonic stem cells (hESCs) has galvanized much interest into their potential application in human Parkinsons disease (PD). We conducted genome-wide, exon-specific expression analyses at three temporally and phenotypically distinct stages of lineage restriction (pluripotent hESCs, multipotent neural precursor cells and terminally differentiated midbrain dopaminergic neurons). We compare these to expression data generated on the same platform from samples isolated from human fetal brain and from human control postmortem samples isolated from the substantia nigra. This comparison highlights the commonalities and differences between neural cells derived from hESCs and their counterparts in the human brain.
No associated publication
Specimen part
View SamplesPrions consist of aggregates of abnormal conformers of cellular prion protein (PrPC). They propagate by recruiting host-encoded PrPC although the critical interacting proteins and the reasons for the differences in susceptibility of distinct cell lines and populations are unknown. We derived a lineage of cell lines with markedly differing susceptibilities, unexplained by PrPC expression differences, to identify such factors. We examined the transcriptomes of prion-resistant revertants, isolated from highly susceptible cells, and identified a gene expression signature associated with susceptibility. Several of these genes encode proteins with a role in extracellular matrix (ECM) remodelling, a compartment in which disease-related PrP deposits. Loss-of-function of nine of these genes significantly increased susceptibility. Remarkably, inhibition of fibronectin 1 binding to integrin 8 by RGD peptide inhibited metalloproteinases (MMP)-2/9 whilst increasing prion propagation rates. This indicates that prion replication may be controlled by MMPs at the ECM in an integrin-dependent manner.
Identification of a gene regulatory network associated with prion replication.
Treatment
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