Introduction:The purpose of this study is to provide athe first global transcriptomic profiling and systems analysis of BoNT-A treated muscle over a one year period. Microarray analysis was performed on rat TA muscle from 4 groups (n=4/group) at 1,4, 12 and 52 weeks after BoNT-A injection and saline injected rats at 12 weeks as control. Fold changes were computed at each time point with respect to control. Results: Dramatic transcriptional adaptation occurs at 1 week with a paradoxical increase in expression of slow and immature isoforms; increased expression of genes in competing pathways of repair and atrophy; impaired mitochondrial biogenesis and increased metal ion imbalance. ECM adaptations occurred at 4weeks to the basal lamina and fibrillar ECM. The muscle transcriptome returned to the unperturbed state 12 weeks post-injection. Conclusion: Transcriptional adaptations resemble denervated muscle albeit some differences. Overall gene expression, across time, correlates with the generally accepted BoNT-A time course.
Systems analysis of transcriptional data provides insights into muscle's biological response to botulinum toxin.
Specimen part
View SamplesAdult zebrafish can completely regenerate their caudal fin following amputation. This complex process is initiated by the formation of an epithelial would cap over the amputation site by 12 hours post amputation (hpa). Once the cap is formed, mesenchymal cells proliferate and migrate from sites distal to the wound plane and accumulate under the epithelial cap forming the blastemal structure within 48 hpa. Blastemal cells proliferate and differentiate, replacing the amputated tissues, which are populated with angiogenic vessels and innervating nerves during the regenerative outgrowth phase which is completed around 14 days post amputation (dpa). Regenerative outgrowth does not occur in TCDD-exposed zebrafish. To identify the molecular pathways that are perturbed by TCDD exposure, male zebrafish were i.p. injected with 50 ng/g TCDD or vehicle and caudal fins were amputated. Regenerating fin tissue was collected at 1, 3 and 5 dpa for mRNA abundance analysis. Microarray analysis and quantitative real time PCR revealed that wound healing and regeneration alone altered the expression of nearly 900 genes by at least two fold between 1 and 5 dpa. TCDD altered the abundance of 370 genes at least two fold. Among these, several known aryl hydrocarbon responsive genes were identified in addition to several genes involved in extracellular matrix composition and metabolism. The profile of misexpressed genes is suggestive of impaired cellular differentiation and extracellular matrix composition potentially regulated by Sox9b.
Regenerative growth is impacted by TCDD: gene expression analysis reveals extracellular matrix modulation.
Sex, Time
View SamplesGene expression in mice skin stimulated with 3 different cytokines
Thymic stromal lymphopoietin is up-regulated in the skin of patients with systemic sclerosis and induces profibrotic genes and intracellular signaling that overlap with those induced by interleukin-13 and transforming growth factor β.
Specimen part
View SamplesExposures to dioxin, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cause a wide array of toxicities in vertebrates and is mostly considered to be mediated through the inappropriate activation of the aryl hydrocarbon receptor (Ahr) signaling pathway. Although transcriptional regulation by Ahr is widely studied, the molecular mechanisms responsible for the adverse outcomes after Ahr activation are largely unknown. To identify the important events downstream of AHR activation that play an actual role in the toxic responses, we employed the zebrafish caudal fin regeneration models since Ahr activation blocks the regenerative process. Zebrafish regenerate their caudal fins by an orchestrated progression of cell migration, differentiation and proliferation controlled by a multitude of signaling pathways. This complex process was exploited as an in vivo platform to identify cross talk between Ahr and other signaling pathways. Global genomic analysis was performed in the larval regenerating fin tissue after exposure to TCDD in order to identify genes differentially regulated after Ahr activation. Comparative toxicogenomic analysis revealed that both adult and larval fins respond to TCDD during regeneration with mis-expression of Wnt signaling pathway members and Wnt target genes.
Crosstalk between AHR and Wnt signaling through R-Spondin1 impairs tissue regeneration in zebrafish.
No sample metadata fields
View SamplesZebrafish have the remarkable ability to regenerate body parts including the heart, spinal cord and fins by a process referred to as epimorphic regeneration. Recent studies have illustrated that similar to adult zebrafish, early life stage-larvae also possess the ability to regenerate the caudal fin. A comparative genomic analysis was used to determine the degree of conservation in gene expression among the regenerating adult caudal fin, adult heart and larval fin. Results indicate that these tissues respond to amputation/injury with strikingly similar genomic responses. Comparative analysis revealed raldh2, a rate-limiting enzyme for the synthesis of Retinoic acid (RA), as one of the highly induced genes across the three regeneration platforms.
Comparative expression profiling reveals an essential role for raldh2 in epimorphic regeneration.
No sample metadata fields
View SamplesThe goal of the study was to compare gene expression of P0 wild-type and P0 Satb2-/- cortices. Total RNAs were isolated from P0 cortices dissected from wild-type and Satb2-/- mice (n=3 for each genotype), following Qiagen RNAeasy kit instruction.Sequence libraries were made following Illumina RNA TruSeq library preparation guide.The libaries were pair-end sequenced (50nt per end). Differentially expressed genes were identified by DESEQ. Overall design: Total RNAs were isolated from P0 cortices (3 control and 3 mutants), and sequenced on Illumina Genome Analyzer
Mutual regulation between Satb2 and Fezf2 promotes subcerebral projection neuron identity in the developing cerebral cortex.
No sample metadata fields
View SamplesEffect of the cytokinin BA on wt and arr1,10,12 mutant seedlings
Type B response regulators of Arabidopsis play key roles in cytokinin signaling and plant development.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Diverse stresses dramatically alter genome-wide p53 binding and transactivation landscape in human cancer cells.
Specimen part, Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Multiple layers of transcriptional regulation by PLZF in NKT-cell development.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Egr2-dependent gene expression profiling and ChIP-Seq reveal novel biologic targets in T cell anergy.
Specimen part, Treatment
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