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GSE43398
Mus musculus
22 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Naive pluripotent embryonic stem cells (ESCs) and embryonic germ cells (EGCs) are derived from the preimplantation epiblast and primordial germ cells (PGCs), respectively. We investigated whether differences exist between ESCs and EGCs, in view of their distinct developmental origins. PGCs are programmed to undergo global DNA demethylation; however, we find that EGCs and ESCs exhibit equivalent global DNA methylation levels. Importantly, inhibition of Erk and Gsk3b by 2i conditions leads to pronounced reduction in DNA methylation in both cell types. This is driven by Prdm14 and is associated with downregulation of Dnmt3a and Dnmt3b. However, genomic imprints are maintained in 2i, and we report derivation of EGCs with intact genomic imprints. Collectively, our findings establish that culture in 2i instills a naive pluripotent state with a distinctive epigenetic configuration that parallels molecular features observed in both the preimplantation epiblast and nascent PGCs.
Publication Title
Naive pluripotency is associated with global DNA hypomethylation.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
IlluminaHiSeq2500
Description
Tuberous sclerosis complex (TSC) is a rare genetic disease characterized by mTOR hyperfunction induced benign tumor growths in multiple organs and neurological symptoms. Because the molecular pathology is highly complex and the etiology poorly understood we employed a defined human neuronal model with a single mTOR activating mutation to dissect the disease-relevant molecular responses driving the neuropathology. TSC2 deficient neural stem cells showed severely reduced neuronal functional maturation and characteristics of astrogliosis instead. Accordingly, transcriptome analysis uncovered an inflammatory response and increased metabolic activity, while ribosome profiling revealed excessive translation of ribosomal transcripts and higher synthesis rates of angiogenic growth factors. Treatment with mTOR inhibitors corrected translational alterations but not transcriptional dysfunction. These results extend our understanding of the molecular pathophysiology of TSC brain lesions, and suggest phenotype-tailored pharmacological treatment strategies. Overall design: Two TSC+/- cell lines and two TSC-/- cell lines were independently generated from wild-type human embryonic stem cells by genome editting with zinc finger nucleases. Two cell lines were handled in the same way but without any known human gene editted and they are used as negative controls. Two independent biological replicates of each of the six cell lines are profiled with ribosome profiling technique.
Publication Title
Genomic analysis of the molecular neuropathology of tuberous sclerosis using a human stem cell model.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 55 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gaucher disease: transcriptome analyses using microarray or mRNA sequencing in a Gba1 mutant mouse model treated with velaglucerase alfa or imiglucerase.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 54 Downloadable Samples
- Illumina HiSeq 2000
Description
The comparative whole genome transcriptome effects of two similar pharmaceuticals, imig or vela, on a Gaucher disease mouse model, 9V/null, were evaluated by two commonly used platforms, mRNA-Seq and microarray. Also, statistical methods, DESeq and edgeR for mRNA-Seq and Mixed Model ANOVA for microarray, were compared for differential gene expression detection. The biological pathways were similar between two platforms. Cell growth and proliferation, cell cycle, heme metabolism, and mitochondrial dysfunction were the most altered functions associated with the disease process. Although the two biopharmaceuticals have a very similar structure and function, imig- and vela- treatment in the mice differentially affected disease-specific pathways indicating the action of the two drugs on the disease process in the visceral tissues of Gaucher mouse model differ significantly at the molecular level. This study provides a comprehensive comparison between the two platforms (mRNA-Seq and microarray) for gene expression analysis and addresses the contribution of the different methods involved in the analysis of such data. The results also provide insights into the differential molecular effects of two similar biopharmaceuticals for Gaucher disease treatment Overall design: 9V/null mice (Gaucher mouse model) were injected weekly via tail vein with 60U/kg/wk of imig or vela for 8 wks. Control 9V/null mice were injected with same volume of saline. Wt mice were untreated. Age and strain matched mice were used for the study. Also, statistical methods, DESeq and edgeR for mRNA-Seq and Mixed Model ANOVA for microarray, were compared for differential gene expression detection. Cell growth and proliferation, cell cycle, heme metabolism, and mitochondrial dysfunction were the most altered functions associated with the disease process. The results also provide insights into the differential molecular effects of two similar biopharmaceuticals for Gaucher disease treatment.
Publication Title
Gaucher disease: transcriptome analyses using microarray or mRNA sequencing in a Gba1 mutant mouse model treated with velaglucerase alfa or imiglucerase.
Sample Metadata Fields
Age, Specimen part, Treatment, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gaucher disease: transcriptome analyses using microarray or mRNA sequencing in a Gba1 mutant mouse model treated with velaglucerase alfa or imiglucerase.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2000
Description
Gaucher disease type 1 is an inborn error of metabolic disease with the defective activity of the lysosomal enzyme acid b-glucosidase (GCase). Enzyme replacement/reconstitution therapy (ERT), infusions with purified recombinant GCases, is efficacious in reversing hematologic, hepatic, splenic, and bony disease manifestations in Gaucher type 1 patients. However, the tissue specific molecular events in Gaucher disease and their response to therapy are not known yet. To explore the molecular events underlying GCase treatment, we evaluated the tissue-specific gene expression profiles and molecular responses in our Gaucher disease mouse model, which were treated with two FDA approved commercially available GCases, imiglucerase (imig) and velaglucerase alfa (vela). Using microarray and mRNA-Seq techniques, differentially expressed genes (DEGs) were identified in the spleen and liver by the direct comparison of imig- vs. vela- treated mice. Among them three gene expression networks were derived from these spleens: 1) cell division/proliferation, 2) hematopoietic system and 3) inflammatory/macrophage response. Our study showed the occurrence of differential molecular pathophysiologic processes in the mice treated with imig compared with vela even though these two biosimilars had the same histological and biochemical efficacy Overall design: 9V/null mice (Gaucher mouse model) were injected weekly via tail vein with 60U/kg/wk of imig or vela for 8 wks. To understand the molecular events underlying GCase treatment, we evaluated the tissue-specific gene expression profiles and molecular responses in our Gaucher disease mouse model, which were treated with two FDA approved commercially available GCases, imiglucerase (imig) and velaglucerase alfa (vela).
Publication Title
Gaucher disease: transcriptome analyses using microarray or mRNA sequencing in a Gba1 mutant mouse model treated with velaglucerase alfa or imiglucerase.
Sample Metadata Fields
Age, Specimen part, Treatment, Subject
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: The aim of this study is to determine the relative expresson levels of mRNA transcripts in wild type platelets Methods: Total RNA was extracted and purified from purified platelets from BALB/c male mice (3 independent samples). Platelet purification was performed as described in Josefsson EC et al, Journal of Experimental Medicine (2011) 208:2017-31. Total RNA (100 ng) was used to generate sequencing libraries for whole transcriptome analysis following Illumina’s TruSeq RNA v2 sample preparation protocol. Completed libraries were sequenced on HiSeq 2000 with TruSeq SBS Kit v3- HS reagents (Illumina) as 100 bp paired-end reads at the Australian Genome Research Facility (AGRF), Melbourne. Reads were aligned to the mouse reference genome mm10 and counts for known genes were obtained using the Rsubread package (version 1.18.0) (Liao et al. 2013; Liao et al. 2014). Overall design: Total RNA was extracted and purified from purified platelets from BALB/c male mice (3 independent samples per population).
Publication Title
Loss of PUMA (BBC3) does not prevent thrombocytopenia caused by the loss of BCL-XL (BCL2L1).
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Analysis of genes that were differentially expressed in axolotl extract reprogrammed tumour xenografts compared to untreated controls. The study provided insight into the biological processes, signalling pathways and gene networks affected by the oocyte extract treatment which resulted in halted tumour growth in mice.
Publication Title
Cancer reversion with oocyte extracts is mediated by cell cycle arrest and induction of tumour dormancy.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 51 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Differencies between groups between pre and post haematopoietic stem cell transplantation children
Publication Title
Genetic Background of Immune Complications after Allogeneic Hematopoietic Stem Cell Transplantation in Children.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
Based on the results of numerous clinical and preclinical analyses, the transcription factor HIF-1a has been identified as an important tumor-promoting factor and is considered to be an attractive target for cancer therapy. To further deconstruct the molecular nature of HIF-1as role in tumorigenesis, we have applied lentiviral shRNA transduction to establish HIF-1a-deficient gastric cancer cells. Interestingly, functional analyses failed to show a significant growth defect of HIF-1a-deficient gastric cancer cells in vitro and in vivo. These observations led us to propose that stable inactivation of HIF-1a resulted in efficient compensation enabling cell growth and, ultimately, tumor progression in a HIF-1a-independent manner. To better understand the mechanisms that control this compensation, we performed transcriptomics of control (scrambled (SCR)) and HIF-1a-deficient (HIF) gastric cancer cells.
Publication Title
Annexin A1 sustains tumor metabolism and cellular proliferation upon stable loss of HIF1A.
Sample Metadata Fields
Specimen part, Cell line
View Samples