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GSE95470
Rattus norvegicus
57 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
We investigated a drug-induced liver injury (DILI) model in rats induced by methapyrilene (MPy) administration. MPy, a former antihistamine and anticholinergic drug, was withdrawn in the 1970ties due to its ability to initiate hepatocarcinogenesis and is now used to induce hepatobiliary injury and biliary epithelial cell hyperplasia. Male Wistar rats (810 weeks old, weighing 170200 g) were randomly assigned to three dosing groups (n=6 per group and time-point) and dosed with MPy at 0, 30 and 80 mg/kg/day by oral gavage. After 4, 8 or 15 days, or after 14 days followed by a recovery period of 10 days (day 24) rats were sacrificed. Increased levels of ALAT, ASAT, AP and -GT as well as bili-t and total bile acids indicated liver damage (AP and GT indicating biliary effects). They were detectable on day 7 at the high dose of 80 mg/kg MPy and persisted until day 15 at end of treatment. Histopathologically, vacuolation and necrosis of the hepatocytes (predominantly in the periportal region) were seen starting on day 3 - especially in animals treated with 80 mg/kg MPy. These findings were accompanied by periportal mononuclear inflammatory cell filtration. Bile duct proliferation, bile duct hyperplasia and increased numbers of mitoses of hepatocytes were evident at all treatment time points. The frequency and severity of these findings increased with dose and duration of the treatment. Gene expression analysis in liver tissues revealed highly significant transcriptional changes in the high dose group, detectable on day 4 and intensifying over time. Besides genes associated with apoptosis (CASP4, CASP12), detoxification (CYB4B) and proliferation (p21, CCNG1) several were related to bile acid metabolism or transport. For example, bile acid exporters OATP1, NTCP, OATP4 and MOAT1/ OATPB as well as the putative bile acid metabolizing enzymes AMACR, BAAT and ACOX2 were found down regulated in response to MPy treatment. In contrast, mRNAs encoding putative bile acid importers MRP2 and ABCC4 / MRP4 were found up regulated. Most of the deregulated levels returned to control values during the recovery phase except OATP1, MOAT1/ OATPB, which remained slightly elevated. Interestingly, OATP4 followed an inverse trend of deregulation after 10 days of recovery, presumably due to overcompensation. Overall, the expression changes found associated with bile acid metabolism or transport could be linked to detected bile acid level alterations in liver and plasma.
Publication Title
Quantitative targeted bile acid profiling as new markers for DILI in a model of methapyrilene-induced liver injury in rats.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Efferent inhibition of cochlear outer hair cells is mediated by nicotinic cholinergic receptors containing alpha9 (a9) and alpha10 subunits. Mice lacking a9 nicotinic subunits fail to exhibit classic olivocochlear responses and are characterized by abnormal synaptic morphology at the base of outer hair cells. To detail molecular changes induced upon the loss of a9 subunit, we sampled cochlear RNA from wild type and a9 null mice at postnatal (P) days spanning periods of synapse formation and maturation (P3, P7, P13 and P60). Our findings point to a delay in cochlear maturation starting at the onset of hearing (P13), as well as an up-regulation of various GABA receptor subunits in adult mice lacking the a9 nicotinic subunit.
Publication Title
Lack of nAChR activity depresses cochlear maturation and up-regulates GABA system components: temporal profiling of gene expression in alpha9 null mice.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Background: Transposable elements are known to influence the regulation of some genes. We aimed to determine which genes show altered gene expression when transposable elements are epigenetically activated.
Publication Title
Genome-wide identification of genes regulated in trans by transposable element small interfering RNAs.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Amniotic fluid (AF) is a complex biological material that provides a unique window into the developing human. Residual AF supernatant contains cell-free fetal RNA. The objective of this study was to develop an understanding of the AF core transcriptome by identifying the transcripts ubiquitously present in the AF supernatant of euploid midtrimester fetuses.
Publication Title
The amniotic fluid transcriptome: a source of novel information about human fetal development.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Whole brain irradiation remains important in the management of brain tumors. Although necessary for improving survival outcomes, cranial irradiation also results in cognitive decline in long-term survivors. A chronic inflammatory state characterized by microglial activation has been implicated in radiation-induced brain injury, and here we present a comprehensive transcriptional profile of irradiated microglia.
Publication Title
Aging-like changes in the transcriptome of irradiated microglia.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
During pregnancy, cells from each fetus travel into the maternal circulation and organs, resulting in the development of microchimerism. Identification of the cell types in this microchimeric population would permit better understanding of possible mechanisms by which they affect maternal health. However, comprehensive analysis of fetal cells has been hampered by their rarity. In this study, we sought to overcome this obstacle by combining flow cytometry with multidimensional gene expression microarray analysis of fetal cells isolated from the murine maternal lung during late pregnancy. Fetal cells were collected from the lungs of pregnant female mice. cDNA was amplified and hybridized to gene expression microarrays. The resulting fetal cell core transcriptome was interrogated using multiple methods including Ingenuity Pathway Analysis, the BioGPS gene expression database, principal component analysis, the Eurexpress gene expression atlas and primary literature. Here we report that small numbers of fetal cells can be flow sorted from the maternal lung, facilitating discovery-driven gene expression analysis. We additionally show that gene expression data can provide functional information about the fetal cells. Our results suggest that fetal cells in the murine maternal lung are a mixed population, consisting of trophoblasts, mesenchymal stem cells and cells of the immune system. The detection of trophoblasts and immune cells in the maternal lung may facilitate future mechanistic studies related to the development of immune tolerance and pregnancy-related complications, such as preeclampsia. Furthermore, the presence and persistence of mesenchymal stem cells in maternal organs may have implications for long-term postpartum maternal health.
Publication Title
Comprehensive analysis of genes expressed by rare microchimeric fetal cells in the maternal mouse lung.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Turner syndrome, a common sex chromosome aneuploidy, has characteristics and malformations associated with the phenotype. Fetal amniotic fluid is a complex biological material that could contribute to the understanding Turner syndrome pathogenesis. Global gene expression analysis of Turner syndrome fetal amniotic fluid supernatant was utilized to identify organ systems and specific genes that may play a role in the pathophysiologic changes that are seen in individuals with Turner syndrome.
Publication Title
Amniotic fluid RNA gene expression profiling provides insights into the phenotype of Turner syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
Illumina Genome Analyzer IIx
Description
We attempted to identify alterations in gene expression that occur during the progression from normal breast to ductal carcinoma in situ (DCIS) with the aim to elucidate significant genes and pathways underlying the premalignant transformation. To determine the expression changes that are common to multiple DCIS models (MCF10.DCIS, SUM102 and SUM225) and normal mammary epithelial cells (MCF10A), we grew the cells in three dimensional overlay culture with reconstituted basement membrane and used the extracted RNA for 76 cycles of deep sequencing (mRNA-Seq) using Illumina Genome Analyzer GAIIx. Analysis of mRNA-Seq results showed 295 consistently differentially expressed transcripts in DCIS models as compared to MCF10A. These differentially expressed genes are associated with a number of signaling pathways such as integrin, fibroblast growth factor and TGFß signaling. Many differentially expressed transcripts in DCIS were found to be involved in cell-cell signaling, cell-cell adhesion and cell proliferation. We further investigated ALDH5A1 gene that encodes for the enzyme, aldehyde dehydrogenase 5A1, which is involved in glutamate metabolism. Further, inhibition of ALDH5A1 with different pharmacological drugs resulted in significant inhibition of cell growth and proliferation in the DCIS models. Overall design: Four cell lines examined: normal mammary epithelial cell line (one sample) and three ductal carcinoma in situ cell lines (three samples). Each sample has two duplicates
Publication Title
RNA-Seq of human breast ductal carcinoma in situ models reveals aldehyde dehydrogenase isoform 5A1 as a novel potential target.
Sample Metadata Fields
Disease, Cell line, Subject
View Samples- Homo sapiens
- 262 Downloadable Samples
- Illumina HiSeq 4000
Description
We report a method for deriving oligodendrocyte lineage cells from human pluripotent stem cells (hPSCs) in three-dimensional (3D) culture called human oligodendrocyte spheroids (hOLS). To characterize oligodendrocyte-lineage cells in hOLS, we isolated O4+ cells by immunopanning and performed deep single cell RNA sequencing. We sequenced 295 cells and compared their profiles to unsorted cells isolated from primary human fetal cortex, primary human adult cortex, and hCS. Clustering of all cells using the t-distributed stochastic neighbor embedding (tSNE) approach revealed a distinct populations of SOX10+ oligodendrocytes, within which the O4+ cells derived from hOLS clustered most closely to oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes from the primary human adult cortical tissue. Additionally, subpopulations of OPCs, newly formed oligodendrocytes, and myelinating oligodendrocytes derived were observed in the hOLS-derived cluster. To further assess the state of oligodendrocyte-lineage cells in hOLS, we performed a Monocle analysis which revealed a spectrum of oligodendrocyte-lineage stages in hOLS ranging from dividing cells that closely resembled primary OPCs to mature cells that closely resembled primary oligodendrocytes. Overall design: Examination of gene expression in single oligodendrocyte-lineage cells derived from human pluripotent stem cells in three-dimensional culture
Publication Title
Differentiation and maturation of oligodendrocytes in human three-dimensional neural cultures.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In order to characterize the differences between second trimester Down syndrome (DS) and euploid fetuses, we compared gene expression in uncultured amniotic fluid supernatant samples. We identified individually differentially expressed genes via paired t-tests in the matched samples, and a set of differentially expressed genes on chromosome 21 using Gene Set Enrichment Analysis. Functional pathway analysis of the resulting genes highlighted the importance of oxidative stress, ion transport, and G-protein signaling in the DS fetuses.
Publication Title
Functional genomic analysis of amniotic fluid cell-free mRNA suggests that oxidative stress is significant in Down syndrome fetuses.
Sample Metadata Fields
Sex, Specimen part
View Samples