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SRP069966
Mus musculus
52 Downloadable Samples
Illumina HiScanSQ
Description
Background & Aims. Glycine N-methyltransferase (GNMT) is an essential regulator of the total transmethylation flux in the mammalian liver. Distinct DNA methylation patterns are characteristic of liver development, hepatic de-differentiation and liver disease progression, processes in which the levels of GNMT decrease dramatically by mechanisms still poorly understood. Interestingly, putative binding sites for the microRNA miRNA-873-5p were identified in the 3´UTR of GNMT suggesting a potential role for miRNA-873-5p in GNMT regulation. Results. We have identified that the hepatic expression of miRNA-873-5p was increased in a cohort of cirrhotic and liver cancer patients associated with a down-regulation of GNMT levels. Moreover, during liver development, hepatic de-differentiation and fibrosis, the elevation of miRNA-873-5p coincided with the reduction of GNMT expression, indicating that miRNA-873-5p specifically targets the expression of GNMT. Under these circumstances, inhibition of miRNA-873-5p induced GNMT levels and decreased global CpG methylation and transmethylation flux. Indeed, reestablishment of GNMT expression by miRNA-873-5p inhibition reduced hepatocyte de-differentiation, and abolished completely the mortality produced after bile duct ligation as a result of decreased proinflamatory and profibrogenic markers. miRNA-873-5p knockdown-mediated antifibrotic effect was significantly blunted if its effect on GNMT was blocked. Conclusion. Taken together, our studies highlight the role of miRNA-873-5p as a key regulator of GNMT expression, paving the way for new therapeutical approaches in liver de-differentiation and fibrosis. Overall design: Genome-wide changes in gene Expression in mouse livers from BDL treated or not with anti-miR-873 were generated by RNAseq.
Publication Title
MiR-873-5p acts as an epigenetic regulator in early stages of liver fibrosis and cirrhosis.
Sample Metadata Fields
Age, Cell line, Treatment, Subject
View Samples- Mus musculus
- 26 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Over the last years, evidence has grown that exposure to air pollution, in addition to impairing lung function and health in individuals of all age, can be linked to negative effects in newborn when present during pregnancy. Data suggests that intrauterine exposure of fetuses (exposure of the mother to air pollution during pregnancy) in fact exerts a negative impact on lung development. However, the means by which exposure during pregnancy affects lung development, have not been studied in depth yet. In this study, we investigated alterations of the transcriptome of the developing lung in a mouse model of gestational and early-life postnatal exposure to urban PM2.5 (from Sao Paulo, Brazil).
Publication Title
Pre- and postnatal exposure of mice to concentrated urban PM<sub>2.5</sub> decreases the number of alveoli and leads to altered lung function at an early stage of life.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Dynamic gene expression in the PSM of vertebrates is critical for the spatial and temporal patterning of somites.
Publication Title
Dynamic CREB family activity drives segmentation and posterior polarity specification in mammalian somitogenesis.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 11 Downloadable Samples
- Affymetrix Genechip Zebrafish ST Genome Array 1.1 (zebgene11st)
Description
Public information is widely available at low cost to animals living in social groups. For instance, bystanders may eavesdrop on signaling interactions between conspecifics and use it to adapt their subsequent behavior towards the observed individuals. This social eavesdropping ability is expected to require specialized mechanisms such as social attention, which selects social information available for learning. To begin exploring the genetic basis of social eavesdropping, we used a previously established attention paradigm in the lab to study the brain gene expression profile of male zebrafish in relation to the attention they have paid towards conspecifics involved or not involved in agonistic interactions. Microarray gene chips were used to characterize their brain transcriptomes based on differential expression of single genes and gene sets. These analyses were complemented by promoter region-based techniques. Using data from both approaches, we further drafted protein interaction networks. Our results suggest that attentiveness towards conspecifics, whether interacting or not, activates pathways linked to neuronal plasticity and memory formation. The network analyses suggested that fos and jun are key players on this response, and that npas4a, nr4a1 and egr4 may also play an important role.
Publication Title
Brain Transcriptomic Response to Social Eavesdropping in Zebrafish (Danio rerio).
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Histone acetylation and other modifications of the chromatin are important regulators of gene expression and, consequently, may contribute to drug-induced behaviors and neuroplasticity. Previous studies have shown that a reduction on histone deacetylase (HDAC) activity results on the enhancement of some psychostimulant-induced behaviors. In the present study, we extend those seminal findings by showing that the administration of the HDAC inhibitor sodium butyrate enhances morphine-induced locomotor sensitization and conditioned place preference. In contrast, this compound has no effects on the development of morphine tolerance and dependence. Similar effects were observed for cocaine and ethanol-induced behaviors. These behavioral changes were accompanied by a selective boosting of a component of the transcriptional program activated by chronic morphine administration that included circadian clock genes and other genes relevant in addictive behavior. Our results support an specific role for histone acetylation and the epigenetic modulation of transcription at a reduced number of biologically relevant loci on non-homeostatic, long lasting, drug-induced behavioral plasticity. To further investigate the molecular bases of sodium butyrate action on long-lasting behavioral responses to morphine, we screened for potential substrates of their interaction by performing a genome-wide comparison of the striatal transcriptome after chronic administration of morphine in the absence or presence of sodium butyrate.
Publication Title
Selective boosting of transcriptional and behavioral responses to drugs of abuse by histone deacetylase inhibition.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Methods of reprogramming somatic cells to an induced pluripotent state (iPSC) have enabled the direct modeling of human disease and ultimately promise to revolutionize regenerative medicine. iPSCs offer an invaluable source of patient-specific pluripotent stem cells for disease modeling, drug screening, toxicology tests and importantly for regenerative medicine, and already have been employed to unmask novel insights into human diseases. While iPSCs can be consistently generated through overexpression of the four Yamanaka Factors OCT4, SOX2, KLF4 and c-MYC (OSKM), reprogrammed cells present worrisome differences with embryonic stem cells in transcriptional and epigenetic profiles, as well as developmental potential and difficulties in cell culturing. A thorough mechanistic understanding of the reprogramming process is critical to overcoming these barriers to the clinical use of iPSC. We have recently published a novel factor combination based on molecules specifically enriched in the metaphase II human oocyte. We have shown that just the overexpression of histone-remodeling chaperone ASF1A and OCT4 in hADFs previously exposed to the oocyte-specific paracrine growth factor GDF9 can reprogram hADFs into pluripotent cells (AO9-iPSCs). Our study contributes to the understanding of the molecular pathways governing somatic cell reprogramming. Here we want to go deeper in the reprogramming mechanisms by understanding the importance of somatic cell origin, and analyzing (and establishing comparison with) the transcriptional and epigenetic characteristics of AO9-iPSCs. As the intrinsic histone chaperone activity of ASF1A and our data indicate, these cells could be closer to the embryonic pluripotent state, with less epigenetic memory, better culture properties and differentiation potential.
Publication Title
Analysis of Menstrual Blood Stromal Cells Reveals SOX15 Triggers Oocyte-Based Human Cell Reprogramming.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genomic landscape of transcriptional and epigenetic dysregulation in early onset polyglutamine disease.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptional dysregulation is an important early feature of polyglutamine diseases. One of its proposed causes is defective neuronal histone acetylation, but important aspects of this hypothesis, such as the precise genomic topography of acetylation deficits
Publication Title
Genomic landscape of transcriptional and epigenetic dysregulation in early onset polyglutamine disease.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We conducted a genome-wide expression analysis of wild-type males using three cell populations isolated from mitotic, meiotic and post-meiotic phases of spermatogenesis in Drosophila melanogaster. Our approach was to directly isolate testis regions enriched with RNAs from each of the three specific germline phases.
Publication Title
Stage-specific expression profiling of Drosophila spermatogenesis suggests that meiotic sex chromosome inactivation drives genomic relocation of testis-expressed genes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Comparing gene expression of cells from the E10.5 limb bud ZPA and the rest of the E10.5 limb bud from Shhgfpcre heterozygotes separated by FACS.
Publication Title
Identification of genes expressed in the mouse limb using a novel ZPA microarray approach.
Sample Metadata Fields
No sample metadata fields
View Samples