Severe malnutrition in young children is associated with signs of hepatic dysfunction such as steatosis and hypoalbuminemia, but its etiology is unknown. To investigate the underlying mechanisms of hepatic dysfunction we used a rat model of malnutrition by placing weanling rats on a low protein or control diet (5% or 20% of calories from protein, respectively) for four weeks. Low protein diet-fed rats developed hypoalbuminemia and severe hepatic steatosis, consistent with the human phenotype. Hepatic peroxisome content was decreased and metabolomic analysis indicated impaired peroxisomal function. Loss of peroxisomes was followed by accumulation of dysfunctional mitochondria and decreased hepatic ATP levels. Fenofibrate supplementation restored hepatic peroxisome abundance and increased mitochondrial fatty acid -oxidation capacity, resulting in reduced steatosis and normalization of ATP and plasma albumin levels. These findings provide important insight into the metabolic
Malnutrition-associated liver steatosis and ATP depletion is caused by peroxisomal and mitochondrial dysfunction.
Sex, Specimen part, Treatment
View SamplesChildhood acute lymphoblastic leukemia (ALL) comprises a large group of genetic subtypes with a favorable prognosis characterized by a TEL-AML1-fusion, hyperdiploidy (>50 chromosomes) or E2A-PBX1 fusion and a smaller group with unfavorable outcome characterized by either a BCR-ABL-fusion, MLL-rearrangement or T-ALL.
A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study.
No sample metadata fields
View SamplesChildhood acute lymphoblastic leukemia (ALL) comprises a large group of genetic subtypes with a favorable prognosis characterized by a TEL-AML1-fusion, hyperdiploidy (>50 chromosomes) or E2A-PBX1 fusion and a smaller group with unfavorable outcome characterized by either a BCR-ABL-fusion, MLL-rearrangement or T-ALL.
A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study.
No sample metadata fields
View SamplesDuring low temperature exposure, temperate plant species increase their freezing tolerance in a process termed cold acclimation. During deacclimation in response to warm temperatures cold acclimated plants lose freezing tolerance and resume growth and development. While considerable effort has been directed toward understanding the molecular and metabolic basis of cold acclimation, much less information is available about the regulation of deacclimation. Here, we report metabolic (GC-MS) and transcriptional (microarrays, qRT-PCR) responses underlying deacclimation during the first 24 h after a shift of cold acclimated Arabidopsis thaliana (Columbia-0) plants to warm temperature. The data revealed a faster response of the transcriptome than of the metabolome and provided evidence for tightly regulated temporal responses at both levels. Metabolically deacclimation is associated with decreasing contents of sugars, amino acids and glycolytic and TCA cycle intermediates, indicating an increased need for carbon sources and respiratory energy production associated with growth resumption under warm temperature conditions. Deacclimation also involves extensive down-regulation of protein synthesis and changes in the metabolism of lipids and cell wall components. Altered hormonal regulation appears particularly important during deacclimation, with changes in the expression of genes related to auxin, gibberellin, brassinosteroid, jasmonate and ethylene metabolisms. Several transcription factor families controlling fundamental aspects of plant development are significantly regulated during deacclimation, emphasizing that loss of freezing tolerance and growth resumption are interrelated processes that are transcriptionally highly interrelated. Expression patterns of some clock oscillator components during deacclimation resembled those under warm conditions, indicating at least partial re-activation of the circadian clock. This study provide the first comprehensive analysis of the regulation of deacclimation in cold acclimated plants. The data indicate cascades of rapidly regulated genes and metabolites that underly the developmental switch resulting in reduced freezing tolerance and the resumption of growth. They constitute a reference dataset of genes, metabolites and pathways that are crucial during the first rapid phase of deacclimation and will be useful for the further analysis of this important but under-researched plant process.
Rapid transcriptional and metabolic regulation of the deacclimation process in cold acclimated Arabidopsis thaliana.
Specimen part, Treatment
View SamplesWe have generated over 80 million 32 nt reads generated from RNA samples isolated from the tip and base of a developing Mo17 leaf. A comparision of these data with the maize AGP resulted in the confirmation of approximately 88% of the maize filtered gene set Keywords: Transcriptome analysis Overall design: Examination of two different RNA samples from two different segments of a developing 3rd leaf
The B73 maize genome: complexity, diversity, and dynamics.
Specimen part, Subject
View SamplesAll above ground organs of higher plants are ultimately derived from shoot apical meristems (SAMs). The SAM exhibits distinctive structural organization, and monocot SAMs such as maize are comprised of two cell layers, a single cell layered tunica (L1) and a corpus (L2). Although recent research has revealed roles of these cell layers in the SAM, intra- and inter-cell-layer signaling networks involved in organ development remain largely unknown except for a few differentially expressed genes. Here, we used Illumnia technology to conduct RNA-seq of L1 and L2 cell layers in maize B73 maize shoot apical meristem. Overall design: Single sequencing library was constructed for L1 and L2 cell layer. Each library was sequenced using 2 lanes on a Solexa flow cell. Processed data file 'ZmB73_4a.53_filtered_genes.fasta' and its README file are linked below as supplementary files. The fasta file contains the gene model ID and corresponding sequence generated from maize genome project. This fasta file was used for the following samples: GSM418173, GSM418174, GSM420173, GSM420174, GSM422828, GSM422829.
The B73 maize genome: complexity, diversity, and dynamics.
Age, Subject
View SamplesHeterosis (hybrid vigor) refers to the superior performance of hybrid progeny relative to their parents. Although widely exploited in agriculture, the mechanisms responsible for heterosis are not well understood. As a monoecious organism, a given maize plant can be used as both male and female parents of crosses. Regardless of the cross direction, the maize inbred lines B73 and Mo17 produce hybrids that substantially out-perform their parents. These reciprocal hybrids differ phenotypically from each other despite having identical nuclear genomes. Consistent with these phenotypic observations, 30-50% of genes were differentially expressed between these reciprocal hybrids. An eQTL experiment conducted to better understand the regulation of gene expression in inbred and hybrid lines detected ~4,000 eQTL associations. The majority of these eQTL act in trans to regulate expression of genes on other chromosomes. Surprisingly, many of the trans-eQTL, when heterozygous, differentially regulated transcript accumulation in a manner consistent with gene expression in the hybrid being regulated exclusively by the paternally transmitted allele. The design of the eQTL experiment controlled for cytoplasmic and maternal effects, suggesting that widespread paternal genomic imprinting contributes to the regulation of gene expression in maize hybrids. Keywords: eQTL, parent-of-origin Overall design: GPL4521 - SAM1.2 (Reciprocal Hybrid Comparison): Six replications of B73xMo17 and Mo17xB73 were grown in growth chambers to tightly control environmental variation. Seeds from each genotype were taken from a single source (ear) for all six replications. Within each replication, genotypes were randomly assigned growth locations. Six healthy seedlings for each genotype and replication were harvested at two weeks of age. For each replication, B73xMo17 and Mo17xB73 were hybridized to the SAM1.2 microarray (GPL4521) using a randomized, alternate dye assignment. GPL3333 - SAM1.1 and GPL3538 - SAM3.0 (eQTL Experiment): Four biological replications of the RIL, B73xRIL, and Mo17xRIL cross-types were planted in growth chambers using seed from a single source for each genotype. Each RIL and its crosses onto B73 and Mo17 were planted using a split-plot design with RIL group (RIL and its cross onto B73 and Mo17) as the whole-plot treatment factor and cross-type (RIL, B73xRIL, and Mo17xRIL) as the split-plot treatment factor. The whole-plot portion of the experiment was designed as a randomized complete block design with four replications carried out on four separate occasions in the same environment. For the split-plot portion of the design, twelve seedlings of each RIL and its crosses were randomized within two adjacent flats in a growth chamber (six healthy seedlings per genotype were randomly chosen and pooled at harvest). For each replication, RIL, B73xRIL, and Mo17xRIL cross-types were hybridized to custom cDNA microarrays using a loop design such that each loop included all pairwise comparisons between the RIL and its crosses with B73 and Mo17. Four biological replications were hybridized to the SAM1.1 (GPL3333) array and two of the four biological replications were hybridized to SAM3.0 (GPL3538). RNA samples were alternately labeled to provide dye balance within each loop and replication. GPL8734 - Gene Expression between two maize reciprocal hybrids Heterosis refers to the enhanced agronomic performance of a hybrid relative to its (usually) inbred parents. We have previously documented widespread differences in gene expression in the B73xMo17 hybrid relative to its inbred parents B73 and Mo17 (Swanson, et al., 2006, PNAS). The reciprocal B73xMo17 and Mo17xB73 hybrids are both highly heterotic, but despite having identical nuclear genomes exhibit statistically significant differences in multiple traits. RNA-seq experiment was conducted to compare the gene expression globally between the two reciprocal hybrids. 1 samples from B73XMo17 and Mo17XB73 RNAs were extracted from a single replication of 14-day-old B73xMo17 and Mo17xB73 seedlings. RNAs were purified using DNaseI treatment followed by cleanup with the RNeasy Plant Mini Kit (Qiagen, Valencia, CA) as per manufacturer instructions. Sequencing library construction was completed using the Illumina mRNA-Seq sample preparation kit. Processed data file 'ZmB73_4a.53_filtered_genes.fasta' and its README file are linked below as supplementary files. The fasta file contains the gene model ID and corresponding sequence generated from maize genome project. This fasta file was used for the following samples: GSM418173, GSM418174, GSM420173, GSM420174, GSM422828, GSM422829.
The B73 maize genome: complexity, diversity, and dynamics.
Age, Specimen part
View SamplesGlucocorticoid resistance (GCR) is defined as an unresponsiveness to the anti-inflammatory properties of glucocorticoids (GCs) and their receptor, the glucocorticoid receptor (GR). It is a serious problem in the management of inflammatory diseases and occurs frequently. The strong pro-inflammatory cytokine TNF induces an acute form of GCR, not only in mice, but also in several cell lines, e.g. in the hepatoma cell line BWTG3, as evidenced by impaired Dexamethasone (Dex)-induced GR-dependent gene expression. We report that TNF has a significant and broad impact on the transcriptional performance of GR, but no impact on nuclear translocation, dimerization or DNA binding capacity of GR. Proteome-wide proximity-mapping (BioID), however, revealed that the GR interactome is strongly modulated by TNF. One GR cofactor that interacts significantly less with the receptor under GCR conditions is p300. NF?B activation and p300 knockdown both reduce transcriptional output of GR, whereas p300 overexpression and NF?B inhibition revert TNF-induced GCR, which is in support of a cofactor reshuffle model. This hypothesis is supported by FRET studies. This mechanism of GCR opens new avenues for therapeutic interventions in GCR diseases Overall design: Examination of GR induced gene expression in 4 conditions (1 control: NI and 3 treated: DEX, TNF, TNFDEX) starting from 3 biological replicates
TNF-α inhibits glucocorticoid receptor-induced gene expression by reshaping the GR nuclear cofactor profile.
Specimen part, Cell line, Treatment, Subject
View SamplesThis experiment was set up in order to identify the (direct) transcriptional targets of the Ethylene Response Factor 115 (ERF115) transcription factor. Because ERF115 expression occurs in quiescent center (QC) cells and strong effects on the QC cells were observed in ERF115 overexpression plants, root tips were harvested for transcript profiling in order to focus on root meristem and QC specific transcriptional targets.
ERF115 controls root quiescent center cell division and stem cell replenishment.
Age, Specimen part
View SamplesMesenchymal progenitor cells can be differentiated in vitro into myotubes that exhibit many characteristic features of primary mammalian skeletal muscle fibers. However, in general, they do not show the functional excitation-contraction coupling or the striated sarcomere arrangement typical of mature myofibers. Epigenetic modifications have been shown to play a key role in regulating the progressional changes in transcription necessary for muscle differentiation. In this study, we demonstrate that treatment of murine C2C12 mesenchymal progenitor cells with 10 M of the DNA methylation inhibitor 5-azacytidine (5AC) promotes myogenesis, resulting in myotubes with enhanced maturity as compared to untreated myotubes. Specifically, 5AC treatment resulted in the upregulation of muscle genes at the myoblast stage while at later stages nearly 50 % of the 5AC-treated myotubes displayed a mature, well-defined sarcomere organization as well as spontaneous contractions that coincided with action potentials and intracellular calcium transients. Both the percentage of striated myotubes and their contractile activity could be inhibited by 20 nM TTX, 10 M ryanodine and 100 M nifedipine, suggesting that action potential-induced calcium transients are responsible for these characteristics. Our data suggest that genomic demethylation induced by 5AC overcomes an epigenetic barrier that prevents untreated C2C12 myotubes from reaching full maturity.
Epigenetics: DNA demethylation promotes skeletal myotube maturation.
Cell line, Treatment
View Samples