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SRP159656
Mus musculus
30 Downloadable Samples
Illumina HiSeq 3000
Description
Metabolic engagement is intrinsic to immune cell function. Prostaglandin E2 (PGE2) has been shown to modulate macrophage activation, yet how PGE2 might affect metabolism is unclear. Here we show that PGE2 causes mitochondrial membrane potential (??m) to dissipate in interleukin-4 activated macrophages (M(IL-4)). Effects on ??m are a consequence of PGE2-initiated transcriptional regulation of genes in the malate-aspartate shuttle (MAS), particularly GOT1. Reduced ??m causes alterations in the expression of 126 voltage regulated genes (VRGs) including Resistin like molecule-a (RELMa), a key marker of M(IL-4), and genes that regulate cell cycle. The transcription factor ETS variant 1 (ETV1) plays a role in the regulation of 38% of the VRGs. These results reveal ETV1 as a ??m-sensitive transcription factor, and ??m as a mediator of mitochondrial-directed nuclear gene expression. Overall design: RNA-seq was performed on bone marrow derived macrophages (triplicate) exposed to IL-4 alone or in combination with PGE2 or Valinomycin plus no stimulation controls. In addition, RNA-seq was performed on bone marrow derived macrophages stimulated in the same way as before, however the transcription factor ETV1 was knocked down.
Publication Title
Mitochondrial Membrane Potential Regulates Nuclear Gene Expression in Macrophages Exposed to Prostaglandin E2.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
In this study, we explored the transcriptomic consequences of strong activation of the Notch pathway in embryonic human neural stem cells and in gliomas. For this we used a forced expression of the Notch intracellular domain (NICD).
Publication Title
Notch1 stimulation induces a vascularization switch with pericyte-like cell differentiation of glioblastoma stem cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 156 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We identified a tumor signature of 5 genes that aggregates the 156 tumor and normal samples into the expected groups. We also identified a histology signature of 75 genes, which classifies the samples in the major histological subtypes of NSCLC. A prognostic signature of 17 genes showed the best association with post-surgery survival time. The performance of the signatures was validated using a patient cohort of similar size
Publication Title
Gene expression-based classification of non-small cell lung carcinomas and survival prediction.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Acetate, propionate and butyrate are the main short-chain fatty acids (SCFAs) that arise from the fermentation of fibers by the colonic microbiota. While many studies focus on the regulatory role of SCFAs, their quantitative role as a catabolic or anabolic substrate for the host has received relatively little attention. To investigate this aspect, we infused conscious mice with physiological quantities of stable isotopes [1-13C]acetate, [2-13C]propionate or [2,4-13C2]butyrate directly into the cecum, which is the natural production site in mice, and analyzed their interconversion by the microbiota as well as their metabolism by the host. Cecal interconversion - pointing to microbial cross-feeding - was high between acetate and butyrate, low between butyrate and propionate and almost absent between acetate and propionate. As much as 62% of infused propionate was used in whole-body glucose production, in line with its role as gluconeogenic substrate. Conversely, glucose synthesis from propionate accounted for 69% of total glucose production. The synthesis of palmitate and cholesterol in the liver was high from cecal acetate (2.8% and 0.7%, respectively) and butyrate (2.7% and 0.9%, respectively) as substrates, but low or absent from propionate (0.6% and 0.0%, respectively). Label incorporation due to chain elongation of stearate was approximately 8-fold higher than de novo synthesis of stearate. Microarray data suggested that SCFAs exert only a mild regulatory effect on the expression of genes involved in hepatic metabolic pathways during the 6h infusion period. Altogether, gut-derived acetate, propionate and butyrate play important roles as substrates for glucose, cholesterol and lipid metabolism.
Publication Title
Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Danio rerio
- 2 Downloadable Samples
- NextSeq 500
Description
In contrast to mammals, zebrafish regenerate heart injuries via proliferation of cardiomyocytes located at the wound border. Here, we show that tomo-seq can be used to identify whole-genome transcriptional profiles of the injury zone, the border zone and the healthy myocardium. Interestingly, the border zone is characterized by the re-expression of embryonic cardiac genes that are also activated after myocardial infarction in mouse and human, including targets of Bone Morphogenetic Protein (BMP) signaling. Endogenous BMP signaling has been reported to be detrimental to mammalian cardiac repair. In contrast, we find that genetic or chemical inhibition of BMP signaling in zebrafish reduces cardiomyocyte dedifferentiation and proliferation, ultimately compromising myocardial regeneration, while bmp2b overexpression is sufficient to enhance it. Our results provide a resource for further studies on the molecular regulation of cardiac regeneration and reveal intriguing differential cellular responses of cardiomyocytes to a conserved signaling pathway in regenerative versus non-regenerative hearts. Overall design: To generate spatially-resolved RNA-seq data for injured zebrafish hearts (3 and 7 days-post-injury), we cryosectioned samples, extracted RNA from the individual sections, and amplified and barcoded mRNA using the CEL-seq protocol (Hashimshony et al., Cell Reports, 2012) with a few modifications. Libraries were sequenced on Illumina NextSeq using 75bp paired end sequencing.
Publication Title
Spatially Resolved Genome-wide Transcriptional Profiling Identifies BMP Signaling as Essential Regulator of Zebrafish Cardiomyocyte Regeneration.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Title: Transcriptome analysis of human endometrial tissues from healthy post-menoupausal women reflecting the endometrial response to 3-weeks treatment with tibolone, E2 and E2+MPA.
Publication Title
Molecular analysis of human endometrium: short-term tibolone signaling differs significantly from estrogen and estrogen + progestagen signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 8 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Metabolic fluxes may be regulated "hierarchically," e.g., by changes of gene expression that adjust enzyme capacities (V(max)) and/or "metabolically" by interactions of enzymes with substrates, products, or allosteric effectors. In the present study, a method is developed to dissect the hierarchical regulation into contributions by transcription, translation, protein degradation, and posttranslational modification. The method was applied to the regulation of fluxes through individual glycolytic enzymes when the yeast Saccharomyces cerevisiae was confronted with the absence of oxygen and the presence of benzoic acid depleting its ATP. Metabolic regulation largely contributed to the approximately 10-fold change in flux through the glycolytic enzymes. This contribution varied from 50 to 80%, depending on the glycolytic step and the cultivation condition tested. Within the 50-20% hierarchical regulation of fluxes, transcription played a minor role, whereas regulation of protein synthesis or degradation was the most important. These also contributed to 75-100% of the regulation of protein levels.
Publication Title
The fluxes through glycolytic enzymes in Saccharomyces cerevisiae are predominantly regulated at posttranscriptional levels.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
We undertook an inter-laboratory effort to generate high-quality quantitative data for a very large number of cellular components in yeast using transcriptome and metabolome analysis. We ensured the high-quality of the experimental data by evaluating a wide range of sampling and measurement techniques. The data were generated for two different yeast strains, each growing under two different growth conditions and based on integrated analysis of the high-throughput data we hypothesize that differences in growth rates and yields on glucose between the two strains are due to differences in protein metabolism.
Publication Title
Integrated multilaboratory systems biology reveals differences in protein metabolism between two reference yeast strains.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Gene 1.1 ST Array (ragene11st)
Description
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
Publication Title
Malnutrition-associated liver steatosis and ATP depletion is caused by peroxisomal and mitochondrial dysfunction.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
Description
RNA polymerase III (Pol III) is an essential enzyme responsible for the synthesis of several small non-coding RNAs, a number of which are involved in mRNA translation. Recessive mutations in POLR3A, encoding the largest subunit of Pol III, cause POLR3-related hypomyelinating leukodystrophy (POLR3-HLD), characterized by deficient central nervous system myelination. Identification of the downstream effectors of pathogenic POLR3A mutations has been so far elusive. Here, we used CRISPR-Cas9 to introduce the POLR3A mutation c.2554A>G (p.M852V) into human cell lines and assessed its impact on Pol III biogenesis, nuclear import, DNA occupancy, transcription, and protein levels. Transcriptomic profiling uncovered a subset of transcripts vulnerable to Pol III hypofunction, including a global reduction in tRNA levels. The brain cytoplasmic BC200 RNA (BCYRN1), involved in translation regulation, was consistently affected in all our cellular models, including patient-derived fibroblasts. Genomic BC200 deletion in an oligodendroglial cell line led to major transcriptomic and proteomic changes, having a larger impact than those of POLR3A mutations. Upon differentiation, mRNA levels of the MBP gene, encoding myelin basic protein, were significantly decreased in POLR3A-mutant cells. Our findings provide the first evidence for impaired Pol III transcription in cellular models of POLR3-HLD and identify several candidate effectors, including BC200 RNA, having a potential role in oligodendrocyte biology and involvement in the disease. Overall design: Gene expression profiling of Pol III transcripts in control and POLR3A-mutated cell lines (HEK293 and MO3.13) using RNA-seq and small RNA-seq; ChIP-seq of FLAG-tagged POLR3A-WT and mutated POLR3A-M852V
Publication Title
Leukodystrophy-associated <i>POLR3A</i> mutations down-regulate the RNA polymerase III transcript and important regulatory RNA <i>BC200</i>.
Sample Metadata Fields
No sample metadata fields
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