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.
Dach2-Hdac9 signaling regulates reinnervation of muscle endplates.
No sample metadata fields
View SamplesWe hypothesize that the observed differences in incidences of pleural and peritoneal malignant mesothelioma (MM) are the result of differences in the direct response of these cell types to asbestos rather than to differences mediated by the in vivo microenvironment. To test this hypothesis, we characterized cellular responses to asbestos in a controlled environment using high-throughput RNA sequence and other assays. Overall design: Examination of asbestos-treated versus untreated mesothelial cells from four cell lines representing two tissue types in culture.
Differential Susceptibility of Human Pleural and Peritoneal Mesothelial Cells to Asbestos Exposure.
No sample metadata fields
View SamplesThe ovary has specialized stromal compartments, including the tunica albuginea, interstitial stroma and theca interna, which develops concurrently with the follicular antrum. To characterize the molecular determinants of these compartments, stroma adjacent to preantral follicles (pre-theca), interstitium and tunica albuginea were laser microdissected (n = 4 per group) and theca interna was dissected from bovine antral follicles (n = 6).
Transcriptome analyses of ovarian stroma: tunica albuginea, interstitium and theca interna.
Specimen part
View SamplesIn this study we examined the influence of seminal plasma on gene expression in human Ect1 ectocervical epithelial cells, and the extent to which recombinant TGF3 elicits comparable changes. Ect1 cells were incubated with recombinant human TGF3 (5 ng/ml), 10% pooled human seminal plasma (v/v), or medium alone for 10h. RNA was reverse transcribed into cDNA and hybridized to Affymetrix GeneChip Human Genome U133 plus 2.0 microarrays (Affymetrix, Santa Clara, CA). Exposure of Ect1 cells to seminal plasma resulted in differential expression of a total of 3955 probe sets, identified using high stringency criteria with MAS 5.0 analysis. These corresponded to 1338 genes up-regulated and 1343 genes down-regulated by seminal plasma. TGF3 treatment of Ect1 cells resulted in differential expression of 884 probe sets, corresponding to 346 up-regulated genes and 229 down-regulated genes. The genes differentially regulated by seminal plasma included several genes associated with cytokinecytokine receptor interaction, TGF signalling, JAK/STAT signalling or VEGF signalling pathways, as specified by the KEGG database. Of 47 genes in these families, 17 (36.1%) were similarly regulated by both seminal plasma and TGF3. These data, together with additional experiments showing all three TGF isoforms can regulate inflammatory cytokine expression in Ect1 cells, identify TGF isoforms as key agents in seminal plasma that signal induction of pro-inflammatory cytokine synthesis in cervical cells.
TGF-β mediates proinflammatory seminal fluid signaling in human cervical epithelial cells.
Cell line, Treatment
View SamplesWe profiled the gene expression/splicing program of normal and hnRNP U-deficient mouse hearts by RNA-seq. Overall design: RNA-seq profiles of control and Hnrnpu mutant hearts at postnatal day 14. Hnrnpu mutant hearts were generated by breeding the Hnrnpu conditional knockout mice with Ckmm-Cre transgenic mice.
hnRNP U protein is required for normal pre-mRNA splicing and postnatal heart development and function.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The response and recovery of the Arabidopsis thaliana transcriptome to phosphate starvation.
Age, Specimen part, Treatment
View SamplesWe provide data from several targeted deletions of transcriptional enhancer clusters within mouse F1 embryonic stem (ES) cells. We targeted these regions for deletion with CRISPR/Cas9 genome editing tools. We demonstrate through heterozygous enhancer cluster deletion and allele specific RNA-seq that enhancer clusters differ in their regulatory activity as the magnitude of the observed change in transcription upon enhancer cluster deletion varies greatly. Overall design: Strand specific RNA-seq after heterozygous or homozygous enhancer cluster deletion in mouse F1 ES cells (M. musculus129 x M. castaneus)
Enhancers and super-enhancers have an equivalent regulatory role in embryonic stem cells through regulation of single or multiple genes.
Cell line, Subject
View SamplesBackground: Over application of phosphate fertilizers in modern agriculture contaminates waterways and disrupts natural ecosystems. Nevertheless, this is a common practice among farmers, especially in developing countries as abundant fertilizers are believed to boost crop yields. The study of plant phosphate metabolism and its underlying genetic pathways is key to discovering methods of efficient fertilizer usage. The work presented here describes the first genome-wide resource on the molecular dynamics underpinning the response and recovery in roots and shoots of Arabidopsis thaliana to phosphate-starvation. Results: Genome-wide profiling revealed minimal overlap between root and shoot transcriptomes suggesting two independent phosphate-starvation regulons. Novel gene expression patterns were detected for over 1000 candidates and were classified as either initial, persistent, or latent responders. Comparative analysis to AtGenExpress identified novel cohorts of genes co-regulated across multiple stimuli. The hormone ABA displayed a dominant role in regulating many phosphate-responsive candidates. Analysis of co-regulation enabled the determination of primary versus redundant members of closely related gene families with respect to phosphate-starvation. Thus, among others, we show that PHO1 acts in shoot, whereas PHO1;H1 is likely the primary regulator in root. Conclusion: Our results uncover a much larger, staged responses to phosphate-starvation than previously described. To our knowledge, this work describes the highest resolution of genome-wide data on plant nutrient stress to date.
The response and recovery of the Arabidopsis thaliana transcriptome to phosphate starvation.
Age, Specimen part, Treatment
View SamplesExtracellular-regulated kinases (ERK1/2 and 5) are known to play important roles in growth and drug resistance of various cancers. Here we show roles of inhibition of ERK1, ERK2, or ERK5 on gene expression profiles of epithelioid malignant mesothelioma (MM) cells (HMESO).
Blocking of ERK1 and ERK2 sensitizes human mesothelioma cells to doxorubicin.
Specimen part, Cell line
View SamplesHuman mesothelial cells (LP9/TERT-1) were exposed to low and high (15 and 75 m2/cm2 dish) equal surface area concentrations of crocidolite asbestos, nonfibrous talc, fine titanium dioxide (TiO2), or glass beads for 8 or 24 h. RNA was then isolated for Affymetrix microarrays, GeneSifter analysis and QRT-PCR. Gene changes by asbestos were concentration- and time-dependent. At low nontoxic concentrations, asbestos caused significant changes in mRNA expression of 29 genes at 8 h and 205 genes at 24 h, whereas changes in mRNA levels of 236 genes occurred in cells exposed to high concentrations of asbestos for 8 h. Human primary pleural mesothelial cells also showed the same patterns of increased gene expression by asbestos. Nonfibrous talc at low concentrations in LP9/TERT-1 mesothelial cells caused increased expression of 1 gene Activating Transcription Factor 3 (ATF3) at 8 h and no changes at 24 h, whereas expression levels of 30 genes were elevated at 8 h at high talc concentrations. Fine TiO2 or glass beads caused no changes in gene expression. In human ovarian epithelial (IOSE) cells, asbestos at high concentrations elevated expression of 2 genes (NR4A2, MIP2) at 8 h and 16 genes at 24 h that were distinct from those elevated in mesothelial cells. Since ATF3 was the most highly expressed gene by asbestos, its functional importance in cytokine production by LP9/TERT-1 cells was assessed using siRNA approaches. Results reveal that ATF3 modulates production of inflammatory cytokines (IL-1, IL-13, G-CSF) and growth factors (VEGF and PDGF-BB) in human mesothelial cells.
Alterations in gene expression in human mesothelial cells correlate with mineral pathogenicity.
Specimen part, Cell line
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