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GSE1419
Mus musculus
30 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Comparison of gene expression between T regulatory and T effector cells isolated from the pancreatic lesion of 3-4 wk old BDC2.5 tg NOD mice
Publication Title
Where CD4+CD25+ T reg cells impinge on autoimmune diabetes.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
Illumina HiSeq 2500
Description
Mammalian oocytes can reprogram somatic cells into totipotent state, which allows animal cloning through somatic cell nuclear transfer (SCNT). However, the great majority of SCNT embryos fail to develop to term due to poorly defined reprogramming defects. Here we demonstrate that histone H3 lysine 9 trimethylation (H3K9me3) in donor nuclei is a major epigenetic barrier that prevents efficient nuclear reprogramming in mouse oocytes. Comparative transcriptome analysis of early embryos revealed reprogramming resistant regions (RRRs) where transcriptional activation at 2-cell embryos is inhibited by SCNT compared to in vitro fertilization (IVF). RRRs significantly overlap with H3K9me3 enrichment in donor somatic cells. Importantly, removal of the H3K9me3 by ectopic expression of an H3K9me3 demethylase Kdm4d in recipient oocytes not only reactivates most RRRs, but also greatly improves development of SCNT embryos. Furthermore, the use of Suv39h1/2-depleted somatic nuclei as donors also greatly improves the development of SCNT embryos. Our study thus reveals H3K9me3 as an epigenetic barrier in SCNT-mediated reprogramming and provides a feasible method for improving mammalian cloning efficiency. Overall design: Here we perform RNA-seq based transcriptome profiling in Donor (cumulus cells), in vitro fertilized (IVF) embryos at 1- and 2-cell stages, somatic cell nuclear transfer (SCNT) embryos at 1- and 2-cell stages, Kdm4d over-expressed 2-cell SCNT embryos, and catalytic domain mutated Kdm4d over-expressed 2-cell SCNT embryos with duplicates.Â
Publication Title
Embryonic development following somatic cell nuclear transfer impeded by persisting histone methylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
FK1706 potentiated nerve growth factor-induced neurite outgrowth, putatively mediated via FKBP-52 and the Ras/Raf/MAPK signaling pathway. It also improved mechanical allodynia accompanied by the recovery of intraepidermal nerve fiber density in a painful diabetic neuropathy in rats.
Publication Title
FK1706, a novel non-immunosuppressive immunophilin ligand, modifies gene expression in the dorsal root ganglia during painful diabetic neuropathy.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
Scope: As a result of population ageing, the number of Alzheimer’s disease (AD) patients has rapidly increased. There are many hypothesises on the pathogenesis of AD, but its detailed molecular mechanism is still unknown, and so no effective preventive or therapeutic measures have been established. Some reports showed a decrease in levels of norepinephrine (NE) has been suspected to be involved in the decline of cognitive function in AD patients and NE concentrations were decreased in postmortem AD patient brains. Tyr-Trp was identified as being the most effective dipeptide in enhancing norepinephrine (NE) synthesis and metabolism. And Tyr-Trp treatment ameliorated the short-term memory dysfunction in AD model mice caused by amyloid beta (Aβ) 25-35. So, the purpose of this study was to investigate the preventive or/and protective effects of Tyr-Trp administration in AD model mice.
Publication Title
Tyr-Trp administration facilitates brain norepinephrine metabolism and ameliorates a short-term memory deficit in a mouse model of Alzheimer's disease.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The mouse anterior-posterior (A-P) axis polarization is preceded by formation of the distal visceral endoderm (DVE). However, the mechanism of the emergence of DVE cells is not well understood. Here, we show by in vitro culturing of embryos immediately after implantation in micro-fabricated cavities (narrow; 90 micro-meter, wide; 180 miro-meter in diameter) that the external mechanical cues exerted on the embryo, i.e. cultured in the narrow cavity, are crucial for DVE formation as well as elongated egg cylinder shape. This implies that these developmental events immediately after implantation are not simply embryo-autonomous processes but require extrinsic mechanical factors. Further whole genome-wide gene expression profiles with DNA microarray revealed that no significant difference of transcripts were evident with or without mechanical cues except DVE-related markers. Thus, we propose that external mechanical cues rather than not specific molecular pathways can trigger the establishment of the A-P axis polarization, which is one of the fundamental proccesses of mammalian embryogenesis.
Publication Title
External mechanical cues trigger the establishment of the anterior-posterior axis in early mouse embryos.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Ovarian clear cell carcinoma (OCCC) shows unique clinical features including an association with endometriosis and poor prognosis. We previously reported that the contents of endometriotic cysts, especially high concentrations of free iron, are a possible cause of OCCC carcinogenesis through iron-induced persistent oxidative stress. In this study, we conducted gene expression microarray analysis using 38 ovarian cancer cell lines and identified genes commonly expressed in both OCCC cell lines and clinical samples, which comprise an OCCC gene signature. The OCCC signature reproducibly predicts OCCC specimens in other microarray data sets, suggesting that this gene profile reflects the inherent biological characteristics of OCCC. The OCCC signature contains known markers of OCCC, such as hepatocyte nuclear factor-1b (HNF-1b) and versican (VCAN), and other genes that reflect oxidative stress. Expression of OCCC signature genes was induced by treatment of immortalized ovarian surface epithelial cells with the contents of endometriotic cysts, indicating that the OCCC signature is largely dependent on the tumor microenvironment. Induction of OCCC signature genes is at least in part epigenetically regulated, as we found hypomethylation of HNF-1b and VCAN in OCCC cell lines. This genomewide study indicates that the tumor microenvironment induces specific gene expression profiles that contribute to the development of distinct cancer subtypes.
Publication Title
Identification of an ovarian clear cell carcinoma gene signature that reflects inherent disease biology and the carcinogenic processes.
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 79 Downloadable Samples
- Illumina HiSeq 2500
Description
Introduction: A considerable proportion of mammalian gene expression undergoes circadian oscillations. Post-transcriptional mechanisms likely make important contributions to mRNA abundance rhythms. Aim: We have investigated how microRNAs contribute to core clock and clock-controlled gene expression using mice in which microRNA biogenesis can be inactivated in the liver. Results: While the hepatic core clock was surprisingly resilient to microRNA loss, whole transcriptome sequencing uncovered widespread effects on clock ouput gene expression. Cyclic transcription paired with microRNA-mediated regulation was thus identified as a widespread phenomenon that affected up to 30% of the rhythmic transcriptome and served to post-transcriptionally adjust the phases and amplitudes of rhythmic mRNA accumulation. However, only a few mRNA rhythms were actually generated by microRNAs. Finally, we pinpoint several microRNAs predicted to act as modulators of rhythmic transcripts, and identify rhythmic pathways particularly prone to microRNA regulation. Conclusion: Our study provides a comprehensive analysis of miRNA activity in shaping hepatic circadian gene expression and can serve as a valuable resource for further investigations into the regulatory roles that miRNAs play in liver gene expression and physiology. Overall design: RNA-Seq of rRNA-depleted total RNAs from two independent full time series around-the-clock of Dicer knockout and control mouse livers
Publication Title
MicroRNAs shape circadian hepatic gene expression on a transcriptome-wide scale.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 46 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Dietary restriction extends lifespan and delays the age-related physiological decline in many species. Intermittent fasting (IF) is one of the most effective dietary restriction regimens that extends lifespan in C. elegans and mammals1,2. In C. elegans, the FOXO transcription factor DAF-16 is implicated in fasting-induced gene expression changes and the longevity response to IF3; however, the mechanisms that sense and transduce fasting-stress stimuli have remained largely unknown. Here we show that a KGB-1/AP1 (activator protein 1) module is a key signalling pathway that mediates fasting-induced transcriptional changes and IF-induced longevity. Our promoter analysis coupled to genome-wide microarray results has shown that the AP-1-binding site, together with the FOXO-binding site, is highly over-represented in the promoter regions of fasting-induced genes. We find that JUN-1 (C. elegans c-Jun) and FOS-1 (C. elegans c-Fos), which constitute the AP-1 transcription factor complex, are required for IF-induced longevity. We also find that KGB-1 acts as a direct activator of JUN-1 and FOS-1, is activated in response to fasting, and, among the three C. elegans JNKs, is specifically required for IF-induced longevity. Our results demonstrate that most fasting-induced upregulated genes, including almost all of the DAF-16-dependent genes, require KGB-1 and JUN-1 function for their induction, and that the loss of kgb-1 suppresses the fasting-induced upregulation of DAF-16 target genes without affecting fasting-induced DAF-16 nuclear translocation. These findings identify the evolutionarily conserved JNK/AP-1 module as a key mediator of fasting-stress responses, and suggest a model in which two fasting-induced signalling pathways leading to DAF-16 nuclear translocation and KGB-1/AP-1 activation, respectively, integrate in the nucleus to coordinately mediate fasting-induced transcriptional changes and IF-induced longevity.
Publication Title
A fasting-responsive signaling pathway that extends life span in C. elegans.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to detail the global gene expression of primary RPE and immortalized RPE.
Publication Title
Identification of a Gene Encoding Slow Skeletal Muscle Troponin T as a Novel Marker for Immortalization of Retinal Pigment Epithelial Cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 14 Downloadable Samples
- IlluminaHiSeq2500
Description
The extremely low efficiency of human embryonic stem cell (hESC) derivation using somatic cell nuclear transfer (SCNT) limits potential application. Blastocyst formation from human SCNT embryos occurs at a low rate and with only some oocyte donors. We previously showed in mice that reduction of histone H3 lysine 9 trimethylation (H3K9me3) through ectopic expression of the H3K9me3 demethylase Kdm4d greatly improves SCNT embryo development. Here we show that overexpression of a related H3K9me3 demethylase KDM4A improves human SCNT, and that, as in mice, H3K9me3 in the human somatic cell genome is an SCNT reprogramming barrier. Overexpression of KDM4A significantly improves the blastocyst formation rate in human SCNT embryos by facilitating transcriptional reprogramming, allowing derivation of NTESCs from all oocyte donors tested using adult AMD patient somatic nuclei donors. This conserved mechanistic insight has potential applications for improving SCNT in a variety of contexts, including regenerative medicine. Overall design: Here we perform RNA-seq based transcriptome profiling in human Donor (fibroblast cells), in vitro fertilized embryos at 8-cell stages (IVF_8Cell), somatic cell nuclear transfer embryos at 8-cell stages (SCNT_8Cell), SCNT assisted by KDM4A 8-cell embryos (SCNT_KDM4A_8Cell). Besides, we also perform RNA-seq in Control human ES cells (CTR_hES) and SCNT assisted by KDM4A derived human ES cells (NTK) with duplicates.Â
Publication Title
Histone Demethylase Expression Enhances Human Somatic Cell Nuclear Transfer Efficiency and Promotes Derivation of Pluripotent Stem Cells.
Sample Metadata Fields
No sample metadata fields
View Samples