Filters
Technology
Platform
GSE40412
Mus musculus
14 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Genome-wide DNA demethylation, including the erasure of genome imprints, in primordial germ cells (PGCs), is critical as a first step for creating the totipotent epigenome in the germ line. Here, we provide evidence that contrary to the prevailing model involving active DNA demethylation, imprint erasure in mouse PGCs occurs in a manner consistent with replication-coupled passive DNA demethylation: PGCs erase imprints during their rapid proliferation with little de novo as well as maintenance DNA methylation potential and no major chromatin alterations. Our findings necessitate the re-evaluation of and provide novel insights into the mechanism of genome-wide DNA demethylation in PGCs.
Publication Title
Replication-coupled passive DNA demethylation for the erasure of genome imprints in mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
IDH2 and NPM1 Mutations Cooperate to Activate Hoxa9/Meis1 and Hypoxia Pathways in Acute Myeloid Leukemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mutations in IDH1 and IDH2 are frequently observed in various cancers, including acute myeloid leukemia (AML). Mutant IDHs convert -ketoglutarate (-KG) to 2-hydroxyglutarate (2-HG), which dysregulates a set of-KG-dependent dioxygenases. To determine whether mutant IDHs are valid targets for cancer therapy, we established a mouse AML model harboring an IDH2 mutation by transplanting mice with nucleophosmin1 (NPM1)+/- mouse hematopoietic stem/progenitor cells that had been co-transduced with four mutant genes (NPMc, IDH2/R140Q, DNMT3A/R882H and FLT3/ITD) that frequently occur simultaneously in human AML patients. IDH2/R140Q is necessary for the engraftment or survival of NPMc+ cells in vivo.Gene-expression analysis indicated that NPMc increased the expression of Hoxa9, and that IDH2/R140Q increased the level of Meis1 and activated the hypoxia pathway in AML cells.Conditional deletion of IDH2/R140Q blocked 2-HG production and maintenance of leukemia stem cells, resulting in survival of the AML mice. IDH2/R140Q reversibly decreased the levels of 5hmC modification and gene expression at some differentiation inducing genes (Ebf1, Pax5 and Spib). These results indicate that the IDH2 mutation is critical for the development and maintenance of AML stem cells, and that mutant IDHs are promising targets for anticancer therapy.
Publication Title
IDH2 and NPM1 Mutations Cooperate to Activate Hoxa9/Meis1 and Hypoxia Pathways in Acute Myeloid Leukemia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
High levels of Hes1 expression are frequently found in BCR-ABL-positive chronic myelogenous leukemia in blast crisis (CML-BC). In mouse bone marrow transplantation (BMT) models, co-expression of BCR-ABL and Hes1 induces CML-BClike disease; however the underlying mechanism remained elusive. Here, based on gene expression analysis, we show that MMP-9 is upregulated by Hes1 in common myeloid progenitors (CMPs). Analysis of promoter activity demonstrated that Hes1 upregulated MMP-9 by activating NF-kB. Analysis of 20 samples from CML-BC patients showed that MMP-9 was highly expressed in three, with two exhibiting high levels of Hes1 expression. Interestingly, MMP-9 deficiency impaired the cobblestone area-forming ability of CMPs expressing BCR-ABL and Hes1 that were in conjunction with a stromal cell layer. In addition, these CMPs secreted MMP-9, promoting the release of soluble Kit-ligand (sKitL) from stromal cells, thereby enhancing proliferation of the leukemic cells. In accordance, mice transplanted with CMPs expressing BCR-ABL and Hes1 exhibited high levels of sKitL as well as MMP-9 in the serum. Importantly, MMP-9 deficiency impaired the development of CML-BClike disease induced by BCR-ABL and Hes1 in mouse BMT models. The present results suggest that Hes1 promotes the development of CML-BC, partly through MMP-9 upregulation in leukemic cells.
Publication Title
Hes1 promotes blast crisis in chronic myelogenous leukemia through MMP-9 upregulation in leukemic cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
RNA sequencing was performed to investigate ionizing radiation-dependent transcriptional change in human pluripotent cells and differentiated cells. Overall design: Examined 3 types of cells (fibroblasts, iPS cells and neural progenitor cells) and 2 types of treatments (non IR or IR), total 6 samples were analyzed.
Publication Title
Reprogramming and differentiation-dependent transcriptional alteration of DNA damage response and apoptosis genes in human induced pluripotent stem cells.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recurrent mutations in ASXL1 are found in various hematological malignancies and are associated with poor prognosis. In particular, ASXL1 mutations are frequently found in patients with hematological malignancies associated with myelodysplasia including myelodysplastic syndromes (MDS), and chronic myelomonocytic leukemia. Although loss-of-function ASXL1 mutations promote myeloid transformation, a large subset of ASXL1 mutations is thought to result in stable truncation of ASXL1. Here we demonstrate that C-terminal truncating ASXL1 mutations (ASXL1-MT) inhibit myeloid differentiation and induce MDS-like disease in mice, displaying all the features of human MDS including multi-lineage myelodysplasia, pancytopenia and occasional progression to overt leukemia. Concerning the molecular mechanisms, ASXL1-MT derepressed expression of Hoxa9 and miR-125a through inhibiting PRC2-mediated methylation of H3K27. miR-125a targeted expression of a surface receptor Clec5a, which was found to supports for myeloid differentiation. In addition, HOXA9 expression was high in MDS patients with ASXL1 mutations while Clec5a expression was generally low in MDS patients. Thus, ASXL1-MT induced MDS-like disease in mice via derepression of Hoxa9 and miR-125a, and Clec5a downregulation. Our data provide evidence for a novel axis of MDS pathogenesis (ASXL1 mutations-upregulation of HoxA9 and miR-125a-downregulation of Clec5a) and implicate both ASXL1 mutants and miR-125a as therapeutic targets in MDS.
Publication Title
Myelodysplastic syndromes are induced by histone methylation–altering ASXL1 mutations.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recurrent mutations in ASXL1 are found in various hematological malignancies and are associated with poor prognosis. In particular, ASXL1 mutations are frequently found in patients with hematological malignancies associated with myelodysplasia including myelodysplastic syndromes (MDS), and chronic myelomonocytic leukemia. Although loss-of-function ASXL1 mutations promote myeloid transformation, a large subset of ASXL1 mutations is thought to result in stable truncation of ASXL1. Here we demonstrate that C-terminal truncating ASXL1 mutations (ASXL1-MT) inhibit myeloid differentiation and induce MDS-like disease in mice, displaying all the features of human MDS including multi-lineage myelodysplasia, pancytopenia and occasional progression to overt leukemia. Concerning the molecular mechanisms, ASXL1-MT derepressed expression of Hoxa9 and miR-125a through inhibiting PRC2-mediated methylation of H3K27. miR-125a targeted expression of a surface receptor Clec5a, which was found to supports for myeloid differentiation. In addition, HOXA9 expression was high in MDS patients with ASXL1 mutations while Clec5a expression was generally low in MDS patients. Thus, ASXL1-MT induced MDS-like disease in mice via derepression of Hoxa9 and miR-125a, and Clec5a downregulation. Our data provide evidence for a novel axis of MDS pathogenesis (ASXL1 mutations-upregulation of HoxA9 and miR-125a-downregulation of Clec5a) and implicate both ASXL1 mutants and miR-125a as therapeutic targets in MDS.
Publication Title
Myelodysplastic syndromes are induced by histone methylation–altering ASXL1 mutations.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
In the present study, we investigated the effect of CBM 588 on lifespan and multiple-stress resistance using Caenorhabditis elegans as a model animal. When adult C. elegans were fed a standard diet of Escherichia coli OP50 or CBM 588, the lifespan of the animals fed CBM 588 was significantly longer than that of animals fed OP50. Moreover, the worms fed CBM 588 were more resistant to certain stressors, including infections with pathogenic bacteria, UV irradiation, and the metal stressor Cu2+. CBM 588 failed to extend the lifespan of the daf-2/IR, daf-16/FOXO and skn-1/Nrf2 mutants. Transcriptional profiling comparing CBM 588-fed and control-fed animals suggested that DAF-16-dependent class II genes were regulated by CBM 588. In conclusion, CBM 588 extends the lifespan of C. elegans probably through regulation of the insulin/IGF-1 signaling (IIS) pathway and the Nrf2 transcription factor, and CBM 588 improves resistance to several stressors in C. elegans. Overall design: Transcriptional profiling of eight-day-old worms that were fed OP50 or CBM 588 for five days, by deep sequencing, using Illumina HiSeq.
Publication Title
<i>Clostridium butyricum</i> MIYAIRI 588 Increases the Lifespan and Multiple-Stress Resistance of <i>Caenorhabditis elegans</i>.
Sample Metadata Fields
Sex, Cell line, Treatment, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The forced expression of Yamanaka factors (Oct3/4, Sox2, Klf4, and c-Myc) reprograms cells into induced pluripotent stem cells (iPSCs) through a series of sequential cell fate conversions. The order and robustness of gene expression changes are highly depended on the Yamanaka factor stoichiometry. We specifically focused on two different reprogramming paths induced by high- and low-Klf4 stoichiometry, which were accomplished by introducing OK+9MS or OKMS polycistronic cassettes, respectively, into mouse embryonic fibroblasts. By comparing these reprograming intermediates with embryonic stem cells (ESCs) and primary keratinocytes, we identified high-Klf4 specific, transiently up-regulated epithelial genes. We found that expression of these epithelial genes was enriched in a TROP2-positive cell population. Moreover, we identified a set of transcription factors which are candidates for the regulation of transiently expressed epithelial genes, and revealed their connection to high-Klf4-specific reprogramming hallmarks.
Publication Title
OVOL1 Influences the Determination and Expansion of iPSC Reprogramming Intermediates.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Zinc-finger genes Fezf1 and Fezf2 encode transcriptional repressors. Fezf1 and Fezf2 are expressed in the early neural stem/progenitor cells and control neuronal differentiation in mouse dorsal telencephalon.
Publication Title
Zinc finger genes Fezf1 and Fezf2 control neuronal differentiation by repressing Hes5 expression in the forebrain.
Sample Metadata Fields
Specimen part
View Samples