To understand the function and regulation of the C. elegans heat shock factor (HSF-1) in larval development, we have used ChIP-seq to analyze the occupancy of HSF1 and RNA Pol II in L2 larvae and young adult (YA) animals grown at 20°C or upon heat shock at 34°C for 30 min. In addition, we have used RNA-seq to analyze the transcriptomes of wild type (N2), hsf-1(ok600) mutants and hsf-1(ok600); rmSi1[hsf-1::gfp] L2 larvae grown at 20°C and characterized the gene expression change by heat shock in wild type (N2) animals at L2 stage. Overall design: Experiment type: RNA-seq. Biological Source: strain: N2, OG576, AM1061; developmental dtage: L2 Larva. Experimental Factors: temperature: 20 degree celsius.
E2F coregulates an essential HSF developmental program that is distinct from the heat-shock response.
Specimen part, Cell line, Subject
View SamplesNeuronal function critically depends on coordinated subcellular distribution of mRNAs. Disturbed mRNA processing and axonal transport has been found in spinal muscular atrophy and could be causative for dysfunction and degeneration of motoneurons. Despite the advances made in characterizing the transport mechanisms of several axonal mRNAs, an unbiased approach to identify the axonal repertoire of mRNAs in healthy and degenerating motoneurons has been lacking. Here we used compartmentalized microfluidic chambers to investigate the somatodendritic and axonal mRNA content of cultured motoneurons by microarray analysis. In axons, transcripts related to protein synthesis and energy production were enriched relative to the somatodendritic compartment. Knockdown of Smn, the protein deficient in spinal muscular atrophy, produced a large number of transcript alterations in both compartments. Transcripts related to immune functions, including MHC class I genes, and with roles in RNA splicing were upregulated in the somatodendritic compartment. On the axonal side, transcripts associated with axon growth and synaptic activity were downregulated. These alterations provide evidence that subcellular localization of transcripts with axonal functions as well as regulation of specific transcripts with nonautonomous functions is disturbed in Smn-deficient motoneurons, most likely contributing to the pathophysiology of spinal muscular atrophy.
Subcellular transcriptome alterations in a cell culture model of spinal muscular atrophy point to widespread defects in axonal growth and presynaptic differentiation.
Specimen part
View SamplesThe transcriptomic changes induced in the human liver cell line HepG2 by 100M menadione, 200M TBH or 50M H2O2 after treatment for 0.5, 1, 2, 4, 6, 8 and 24h.
Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach.
Cell line
View SamplesThe transcriptomics changes induced in the human liver cell line HepG2 by low and high doses of acetaminophen and solvent controls after treatment for 4 time points (12h, 24h, 48h and 72h)
Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain.
Specimen part, Cell line, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Extensive temporal transcriptome and microRNA analyses identify molecular mechanisms underlying mitochondrial dysfunction induced by multi-walled carbon nanotubes in human lung cells.
Specimen part, Treatment
View SamplesUnderstanding toxicity pathways of engineered nanomaterials (ENM) has recently been brought forward as a key step in 21st century ENM risk assessment. Molecular mechanisms linked to phenotypic end points is a step towards the development of toxicity tests based on key events, which may allow for grouping of ENM according to their mechanisms of action. This study identified molecular mechanisms underlying mitochondrial dysfunction in human bronchial epithelial BEAS 2B cells following exposure to one of the most studied multi-walled carbon nanotubes (MWCNTs; Mitsui-7). Asbestos was used as a positive control and a non-carcinogenic glass wool material was included as a negative fibre control. Decreased mitochondrial membrane potential (MMP) was observed for MWCNTs at a biologically relevant dose (0.25 g/cm2) and for asbestos at 2 g/cm2, but not for glass wool. Extensive temporal transcriptomic and microRNA expression analyses identified a 330-gene signature related to MWCNT- and asbestos-induced MMP. Fourty-nine of the MMP-associated genes showed highly similar expression patterns over time (six time points) and the majority was found to be regulated by two transcription factors strongly involved in mitochondrial homeostasis, APP and NRF1. In addition, four miRNAs were associated with MMP and one of them, miR-1275, was found to negatively correlate with a large part of the MMP-associated genes. Cellular processes such as gluconeogenesis, glucose metabolism, mitochondrial LC-fatty acid -oxidation and spindle microtubule function were enriched among the MMP-associated genes and miRNAs. These results are expected to be useful in the identification of key events in ENM-related toxicity pathways for the development of molecular screening techniques.
Extensive temporal transcriptome and microRNA analyses identify molecular mechanisms underlying mitochondrial dysfunction induced by multi-walled carbon nanotubes in human lung cells.
Specimen part, Treatment
View SamplesWe used microarrays to identify genes differentially expressed between mouse RUNX2 -/- and wt embryonic humeri at stage E14.5
Detection of novel skeletogenesis target genes by comprehensive analysis of a Runx2(-/-) mouse model.
No sample metadata fields
View SamplesPurpose: Epidemiological and intervention studies have attempted to link the health effects of a diet rich in fruits and vegetables with the consumption of polyphenols and their impact in neurodegenerative diseases. Studies have shown that polyphenols can cross the intestinal barrier and reach concentrations in the bloodstream able to exert effects in vivo. However, the effective uptake of polyphenols in the brain is still regarded with some reservations. Here we describe a combination of approaches to examine the putative transport of blackberry-digested polyphenols (BDP) across the blood-brain barrier (BBB) and ultimate evaluation of their beneficial effects.
Blood-brain barrier transport and neuroprotective potential of blackberry-digested polyphenols: an in vitro study.
Sex, Specimen part, Cell line, Race
View SamplesDuring embryogenesis, enhancer-promoter interactions control gene transcriptional activation. These interactions can be tissue-specific or tissue-invariant and occur mostly within larger insulated regulatory domains called Topologically Associating Domains (TADs). Boundary elements, which delineate the extent of TADs, frequently interact with each other and have been associated with constitutive transcription and CTCF/Cohesin binding. In this work, we set out to investigate the regulatory role of a tissue-invariant, preformed interaction between two boundaries that involve the Shh gene and its unique limb enhancer, the ZRS, located one megabase away. Using CRISPR/Cas9 we specifically perturb CTCF binding sites or constitutive transcription at the ZRS-containing boundary, without altering the enhancer sequence. Using capture-HiC (cHiC) we show that both types of perturbation result in altered preformed chromatin interactions and lead to a reduction of Shh expression in developing limb buds. Finally, we demonstrate that the disruption of the chromatin structure in combination with a hypomorphic ZRS allele results in a dramatic Shh loss- of- function and digit agenesis. We thus propose that preformed chromatin structures can ensure stable enhancer promoter communication during development and robustness of gene transcriptional activation. Overall design: We performed transcriptome analysis to confirm the complete loss of the Lmbr1 transcript due to the deletion of its promoter and to detect other potential non-coding transcripts at the locus.
Preformed chromatin topology assists transcriptional robustness of <i>Shh</i> during limb development.
Cell line, Subject
View SamplesAdipose stroma in the mouse mammary gland undergoes remodeling throughout the 5 stages of development. These include nulliparous (virgin;never been pregnant), pregnant, lactating, involuting and regressed.
Pregnancy-associated breast cancers are driven by differences in adipose stromal cells present during lactation.
Specimen part
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