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GSE95489
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Purpose: MetS consist of five risk factors: elevated blood pressure and fasting glucose, visceral obesity, dyslipidemia and hypercholesterinemia. The physiological impact of lipid metabolism indicated as visceral obesity and hepatic lipid accumulation is still under debate. One major cause of disturbed lipid metabolism might be dysfunction of cellular organelles controlling energy homeostasis, i.e. mitochondria and peroxisomes.
Publication Title
Alteration of Liver Peroxisomal and Mitochondrial Functionality in the NZO Mouse Model of Metabolic Syndrome.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Background and aim: The Insulin-like growth factor (IGF) axis is increasingly suggested to be involved in fatty liver disease and progression. We identified IGFBP2 as transcriptional regulatory effect network in liver steatosis and conducted a translational approach of its role in liver pathology from mouse to human, and whether it is influenced by conventional clinical intervention that mitigate hepatic steatosis. Methods: Primary hepatocytes from either C57Bl6 controls, alb-SREBP-1c mice with moderate transgene induced hepatic lipid accumulation or aP2-SREBP-1c mice with massive ectopic hepatic lipid accumulation, were analyzed to identify regulatory networks based on differentially regulated hepatic gene expression. In a translational approach, serum of morbidly obese patients with and without diabetes and biopsy-proven NAFLD were used for ELISA-based validation of mouse data. Moreover, sera of patients undergoing intervention were analyzed and correlated to liver fat content. Results: Comparative knowledge-based transcriptome analysis identified IGFBP2 as top score regulatory effect network between moderate and aggravated fatty liver in mouse models. The reduced expression of IGFBP2 in aP2-SREPB-1c progressed fatty liver associated with Igfbp2 promoter hypermethylation. Reduced secretion of IGFBP2 from aP2-SREBP-1c hepatocytes was reflected in the circulation of the animals. In this phenotype, reductions of IGFBP2 were accompanied by reduced fatty acid oxidation and increased methyltransferase and SIRT activity. Physiologically, IGFBP2 has no direct impact on lipid metabolism but might modulate IGF1 action on de novo lipogenesis. In humans, IGFBP2 levels declined from non-obese men to morbidly obese men with NAFLD and NASH. In intervention study reductions in liver fat correlated with restoration of IGFBP2 serum levels to values found in healthy individuals in morbidly obese patients following bariatric surgery. Conclusion: In hepatic metabolism changes of IGFBP2 abundance is connected to lipid metabolism whereas changes in IGFBP2 secretion were directly reflected in the circulation. IGFBP2 serum concentration correlates with the degree of fatty liver, which seems to be related to plasticity of the adipose tissue. These data provide IGFBP2 as a potential non-invasive biomarker for fatty liver disease directly reflecting the degree of impaired liver function with the potential to indicate progressed fatty liver disease.
Publication Title
Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Monocyte chemoattractant protein 1 (MCP-1/CCL2) is critically involved in directing the migration of blood monocytes to sites of inflammation. Consequently, excessive MCP-1 secretion has been linked to many (auto)inflammatory diseases, whereas a lack of expression severely impairs immune responsiveness. We demonstrate that the atypical inhibitor of NF-B (IB), a transcriptional co-activator required for the selective expression of a subset of NF-B target genes, is a key activator of the Ccl2 gene. IB-deficient macrophages exhibited impaired secretion of MCP-1 when challenged with diverse inflammatory stimuli, such as lipopolysaccharide or peptidoglycan. These findings were reflected at the level of Ccl2 gene expression, which was tightly coupled to the presence of IB. Moreover, mechanistic insights acquired by chromatin immunoprecipitation demonstrate that IB is directly recruited to the proximal promoter region of the Ccl2 gene and required for histone H3K9 trimethylation. Finally, IB-deficient mice showed significantly impaired MCP-1 secretion and monocyte infiltration in an experimental model of peritonitis. Together, these findings suggest a distinguished role of IB in mediating the targeted recruitment of monocytes in response to local inflammatory events.
Publication Title
IκBζ is a transcriptional key regulator of CCL2/MCP-1.
Sample Metadata Fields
Sex, Specimen part
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Analysis of the transcriptomes of nearly ripe siliques (18-19 DAP) of the rdo2-1, rdo3 and hub1-2 (rdo4) mutants in comparison with wild-type Ler, using Affymetrix GeneChip Arabidopsis ATH1 Genome Array.
Publication Title
Identification of the Arabidopsis REDUCED DORMANCY 2 gene uncovers a role for the polymerase associated factor 1 complex in seed dormancy.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 46 Downloadable Samples
Illumina HiSeq 2000
Description
Determine allele level expression in hybrid mice of different ages Overall design: RNASeq - HybridMouseDRN
Publication Title
Diverse Non-genetic, Allele-Specific Expression Effects Shape Genetic Architecture at the Cellular Level in the Mammalian Brain.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Sus scrofa
- 18 Downloadable Samples
- Porcine Gene 1.0 ST Array (porgene10st)
Description
The hypothesis was tested that insect meal (IM) as protein source influences intermediary metabolism of growing pigs. To test this, 5-week-old crossbreed pigs were randomly assigned to 3 groups of 10 pigs each with similar body weights (BW) and fed isonitrogenous diets either without (CON) or with 5 % IM (IM5) or 10 % IM (IM10) from Tenebrio molitor L. for 4 weeks and skeletal muscle was analyzed using transcriptomics. Transcriptomics of skeletal muscle revealed a total of 198 transcripts differentially expressed between IM10 and CON.
Publication Title
Comprehensive evaluation of the metabolic effects of insect meal from <i>Tenebrio molitor</i> L. in growing pigs by transcriptomics, metabolomics and lipidomics.
Sample Metadata Fields
Sex, Specimen part
View Samples- Sus scrofa
- 18 Downloadable Samples
- Porcine Gene 1.0 ST Array (porgene10st)
Description
The hypothesis was tested that insect meal (IM) as protein source influences intermediary metabolism of growing pigs. To test this, 5-week-old crossbreed pigs were randomly assigned to 3 groups of 10 pigs each with similar body weights (BW) and fed isonitrogenous diets either without (CON) or with 5 % IM (IM5) or 10 % IM (IM10) from Tenebrio molitor L. for 4 weeks and liver was analyzed using transcriptomics. Transcriptomics of the liver revealed a total of 166 transcripts differentially expressed between IM10 and CON.
Publication Title
Comprehensive evaluation of the metabolic effects of insect meal from <i>Tenebrio molitor</i> L. in growing pigs by transcriptomics, metabolomics and lipidomics.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 84 Downloadable Samples
- NextSeq 500, Illumina HiSeq 2000
Description
The preoptic area (POA) of the hypothalamus is known to be crucial for sleep generation, but the spatial intermingling of sleep- and wake-promoting neurons makes it difficult to dissect the sleep control circuit. Here we identified a population of POA sleep-promoting neurons based on their projection target. Using a lentivirus for retrograde labeling with channelrhodopsin-2 (ChR2) followed by optogenetic manipulation and recording, we found that the POA GABAergic neurons projecting to the tuberomammillary nucleus (TMN) are both sleep active and sleep promoting. Cell type- and projection-specific rabies tracing revealed the presynaptic inputs to these neurons, including an amygdala GABAergic input that promotes wakefulness. Using single-cell RNA-seq, we identified several molecular markers for these neurons, and optogenetic activation of the POA neurons labeled by these markers confirmed their sleep-promoting effects. Together, these findings define a group of sleep-promoting neurons functionally, anatomically, and genetically. Overall design: Single-cell RNA-Seq of retrogradely-labeled POA neurons projecting to the tuberomammillary nucleus (TMN).
Publication Title
Identification of preoptic sleep neurons using retrograde labelling and gene profiling.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 78 Downloadable Samples
- Illumina HiSeq 2500, Illumina HiSeq 3000, NextSeq 500
Description
Interrogation and control of cellular fate and function using optogenetics is providing revolutionary insights into biology. Optogenetic control of cells is achieved by coupling genetically encoded photoreceptors to cellular effectors and enables unprecedented spatiotemporal control of signaling processes. Here, a fast and reversibly switchable photoreceptor is used to tune the mechanical properties of polymer materials in a fully reversible, wavelength-specific, and dose- and space-controlled manner. By integrating engineered cyanobacterial phytochrome 1 into a polyethylene glycol matrix, hydrogel materials responsive to light in the cell-compatible red/far-red spectrum are synthesized. These materials are applied to study in human mesenchymal stem cells how different mechano-signaling pathways respond to changing mechanical environments, and to control the migration of primary immune cells in 3D. This optogenetics-inspired matrix allows addressing fundamental questions of how cells react to dynamic mechanical environments. Further, remote control of such matrices could create new opportunities for tissue engineering or provide a basis for optically stimulated drug depots. Overall design: Analysis of global gene expression changes due to differences in the mechanical properties of the phytochrome-based hydrogels
Publication Title
Phytochrome-Based Extracellular Matrix with Reversibly Tunable Mechanical Properties.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 36 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Mantle cell lymphoma (MCL) is a mature B-cell lymphoma characterized by poor clinical outcome. Recent studies revealed the importance of BCR signaling in maintaining MCL survival. However, it remains unclear which role MALT1, an essential component of the CARD11-BCL10-MALT1 (CBM) complex that transfers BCR signaling to the NF-kB pathway, plays in the biology of MCL. Here we show that a subset of MCLs is addicted to MALT1, as its inhibition by either RNA or pharmacologic interference induced cytotoxicity both in vitro and in vivo. Gene expression profiling following MALT1 inhibition demonstrated that MALT1 controls a MYC-driven gene expression network predominantly through increased MYC protein stability. Thus our analyses identify a previously unappreciated regulatory mechanism of MYC expression. Investigating primary mouse splenocytes, we could demonstrate that MALT1 induced MYC regulation is not restricted to MCL, but represents a common mechanism of MYC regulation. MYC itself is pivotal for MCL survival as its downregulation and pharmacologic inhibition induced cytotoxicity in all MCL models. Collectively, these results provide a strong mechanistic rationale to investigate the therapeutic efficacy in targeting the MALT1-MYC axis in MCL patients.
Publication Title
B-cell receptor-driven MALT1 activity regulates MYC signaling in mantle cell lymphoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples