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GSE153298
Mus musculus
9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Chimeric mice with humanized livers are considered a useful animal model for predicting human drug metabolism and toxicity. In this study, the characteristics of fresh h-hepatocytes (cFHHs, PXB-cells®) isolated from chimeric mice (PXB-mice®) were evaluated in vitro to confirm their utility for drug development. The cFHHs cultured at high density (2.13 × 10^5 cells/cm2) displayed stable production of human albumin and cytochrome P450 (CYP) 3A activities for at least 21 days. The mRNA expression levels of 10 of 13 CYPs, UDP-glucuronosyltransferase (UGP), and transporters were maintained at >10% of the levels of freshly isolated cFHHs after 21 days. From 7-days cultured cFHHs at high density, many bile canaliculi were observed between cFHHs, and the accumulation of multidrug resistance-associated protein (MRP2) and bile salt export pump (BSEP) substrates in these bile canaliculi was clearly inhibited by cyclosporin A.
Publication Title
Culture density contributes to hepatic functions of fresh human hepatocytes isolated from chimeric mice with humanized livers: Novel, long-term, functional two-dimensional in vitro tool for developing new drugs.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 2 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
The Shumiya cataract rat (SCR) is a model for hereditary cataract. Two-third of these rats develop lens opacity within 10-11-weeks. Onset of cataract is attributed to the synergetic effect of lanosterol synthase (Lss) and farnesyl-diphosphate farnesyltransferase 1 (Fdft1) mutant alleles that lead to cholesterol deficiency in the lenses, which in turn adversely affects lens biology including the growth and differentiation of lens epithelial cells (LECs). Nevertheless, the molecular events and changes in gene expression associated with the onset of lens opacity in SCR is poorly understood.
Publication Title
Identification of Differential Gene Expression Pattern in Lens Epithelial Cells Derived from Cataractous and Noncataractous Lenses of Shumiya Cataract Rat.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
We found constitutive upregulation and higher degree induction of drug metabolism and disposition-related genes in a three-dimensional HepG2 culture. The upregulated genes are those believed to be regulated by different regulatory factors. The global gene expression analysis by Affymetrix GeneChip indicated that altered expressions of microtubule-related genes may change expressed levels of drug metabolism and disposition genes. Stabilization of the microtubule molecules with docetaxel, a tubulin stabilizing agent, in the two-dimensional culture showed gene expression patterns similar to those in the three-dimensional culture, indicating that culture environment affects drug metabolism functions in HepG2 cells.
Publication Title
Global gene expression changes including drug metabolism and disposition induced by three-dimensional culture of HepG2 cells-Involvement of microtubules.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 34 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
To examine irreversible changes in the developing brain following seizures, juvenile inbred mice were intraperitoneally injected with kainate and nicotine.
Publication Title
Increased expression of the lysosomal protease cathepsin S in hippocampal microglia following kainate-induced seizures.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Genome-wide expression analysis of two circadian oscillatory mechanisms in the mouse liver
Publication Title
Genome-wide expression analysis reveals 100 adrenal gland-dependent circadian genes in the mouse liver.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
Illumina HiSeq 2000
Description
Insulin-producing beta cells become dedifferentiated during diabetes progression. An impaired ability to select substrates for oxidative phosphorylation, or metabolic inflexibility, sets the stage for progression from beta cell dysfunction to beta cell dedifferentiation. In this study, we sought to isolate and functionally characterize failing beta cells, as a preliminary step to identify pathways to reverse dedifferentiation. Using various experimental models of diabetes, we found a striking enrichment in the expression of aldehyde dehydrogenase 1 isoform A3 (ALDH+) as beta cells become dedifferentiated. Flow-sorted ALDH+ islet cells demonstrate impaired glucose-induced insulin secretion, are depleted of Foxo1 and MafA, and include a Neurogenin3-positive subset. RNA sequencing analysis demonstrates that ALDH+ cells are characterized by: (i) impaired oxidative phosphorylation and mitochondrial complex I, IV, and V; (ii) activated RICTOR; and (iii) progenitor cell markers. We propose that impaired mitochondrial function marks the progression from metabolic inflexibility to dedifferentiation in the natural history of beta cell failure. Overall design: RNA-Sequencing analysis of 2 different cell types in 2 different genotype categories.
Publication Title
Aldehyde dehydrogenase 1a3 defines a subset of failing pancreatic β cells in diabetic mice.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
To assess RNA regulation in FALS for gene expression and alternative processing of RNA in the motor neuron precurssors (MPCs)
Publication Title
Establishment of In Vitro FUS-Associated Familial Amyotrophic Lateral Sclerosis Model Using Human Induced Pluripotent Stem Cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
We performed microarray analysis in order to evaluate the combination effect of the mitochondrial matrix chaperone inhibitor gamitrinib-triphenylphosphonium (G-TPP) and Liver X receptor agonist LXR623 on gene expression in stem cell like glioma cells (NCH644).
Publication Title
Activation of LXR Receptors and Inhibition of TRAP1 Causes Synthetic Lethality in Solid Tumors.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
The role of PPAR in gene regulation in mouse liver is well characterized. However, less is known about the effect of PPAR activation in human liver. The aim of the present study was to better characterize the impact of PPAR activation on gene regulation in human liver by combining transcriptomics with the use of hepatocyte humanized livers. To that end, chimeric mice containing hepatocyte humanized livers were given an oral dose of 300 mg/kg fenofibrate daily for 4 days. Livers were collected and analysed by hematoxilin and eosin staining, qPCR, and transcriptomics. Transcriptomics data were compared with existing datasets on fenofibrate treatment in normal mice. The human hepatocytes exhibited excessive lipid accumulation. Fenofibrate increased the size of the mouse but not human hepatocytes, and tended to reduce steatosis in the human hepatocytes. Quantitative PCR indicated that induction of PPAR targets by fenofibrate was less pronounced in the human hepatocytes than in the residual mouse hepatocytes. Transcriptomics analysis indicated that, after filtering, a total of 282 genes was significantly different between fenofibrate- and control-treated mice (P<0.01). 123 genes were significantly lower and 159 genes significantly higher in the fenofibrate-treated mice, including many established PPAR targets such as FABP1, HADHB, HADHA, VNN1, PLIN2, ACADVL and HMGCS2. According to gene set enrichment analysis, fenofibrate upregulated interferon/cytokine signaling-related pathways in hepatocyte humanized liver, but downregulated these pathways in normal mouse liver. Also, fenofibrate downregulated pathways related to DNA synthesis in hepatocyte humanized liver but not in normal mouse liver. The results support the major role of PPAR in regulating hepatic lipid metabolism, and underscore the more modest effect of PPAR activation on gene regulation in human liver compared to mouse liver. The data suggest that PPAR may have a suppressive effect on DNA synthesis in human liver, and a stimulatory effect on interferon/cytokine signalling.
Publication Title
The whole transcriptome effects of the PPARα agonist fenofibrate on livers of hepatocyte humanized mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Total RNA from trichomes of fifth and sixth rosette leaves of three-week-old wild-type and gtl1-1 mutants (Figure 3B) were extracted. We found a total number of 1,759 genes, corresponding to 1,694 probes on the ATH1 chip, that show differential expression of at least 1.3-fold. Out of these 1,694 genes, 47.2% are positively regulated and 52.8% are negatively regulated by GTL1.
Publication Title
Transcriptional repression of the APC/C activator CCS52A1 promotes active termination of cell growth.
Sample Metadata Fields
Specimen part
View Samples