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GSE93923
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Rearrangements involving the NUP98 gene resulting in fusions to several partner genes occur in acute myeloid leukemia and myelodysplastic syndromes. This study demonstrates that the second FG repeat domain of the NUP98 moiety of the NUP98-HOXA9 fusion protein is important for its cell immortalization and leukemogenesis activities. We demonstrate that NUP98-HOXA9 interacts with MLL via this FG repeat domain and that, in the absence of MLL, NUP98-HOXA9-induced cell immortalization and leukemogenesis are severely inhibited. Molecular analyses indicate that MLL is important for the recruitment of NUP98-HOXA9 to the HOXA locus and for NUP98-HOXA9-induced HOXA gene expression. Our data indicate that MLL is crucial for NUP98-HOXA9 leukemia initiation.
Publication Title
MLL is essential for NUP98-HOXA9-induced leukemia.
Sample Metadata Fields
No sample metadata fields
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- Homo sapiens
- 9 Downloadable Samples
Illumina HiSeq 2000
Description
We have analyzed publicly available K562 Hi-C data, which enables genome-wide unbiased capturing of chromatin interactions, using a Mixture Poisson Regression Model to define a highly specific set of interacting genomic regions. We integrated multiple ENCODE Consortium resources with the Hi-C data, using DNase-seq data and ChIP-seq data for 46 transcription factors and 8 histone modifications. We classified 12 different sets (clusters) of interacting loci that can be distinguished by their chromatin modifications and which can be categorized into three types of chromatin hubs. The different clusters of loci display very different relationships with transcription factor binding sites. As expected, many of the transcription factors show binding patterns specific to clusters composed of interacting loci that encompass promoters or enhancers. However, cluster 6, which is distinguished by marks of open chromatin but not by marks of active enhancers or promoters, was not bound by most transcription factors but was highly enriched for 3 transcription factors (GATA1, GATA2, and c-Jun) and 3 chromatin modifiers (BRG1, INI1, and SIRT6). To validate the identification of the clusters and to dissect the impact of chromatin organization on gene regulation, we performed RNA-seq analyses before and after knockdown of GATA1 or GATA2. We found that knockdown of the GATA factors greatly alters the expression of genes within cluster 6. Our work, in combination with previous studies linking regulation by GATA factors with c-Jun and BRG1, provide genome-wide evidence that Hi-C data identifies sets of biologically relevant interacting loci. Overall design: RNA-seq of control, siGATA1 and siGATA2 K562 cells
Publication Title
Integration of Hi-C and ChIP-seq data reveals distinct types of chromatin linkages.
Sample Metadata Fields
Cell line, Subject
View Samples- Drosophila melanogaster
- 30 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Regeneration of fragmented Drosophila imaginal discs occurs in an epimorphic manner, involving local cell proliferation at the wound site. Following disc fragmentation, cells at the wound site activate a restoration program through wound healing, regenerative cell proliferation and repatterning of the tissue. However, the interplay of signaling cascades, driving these early reprogramming steps, is not well understood. Here we profiled the transcriptome of regenerating cells in the early phase within twenty-four hours after wounding. We found that JAK/STAT signaling becomes activated at the wound site and promotes regenerative cell proliferation in cooperation with Wingless (Wg) signaling. In addition, we demonstrated that the expression of Drosophila insulin-like peptide 8 (dilp8), which encodes a paracrine peptide to delay the onset of pupariation, is controlled by JAK/STAT signaling in early regenerating discs. Our findings suggest that JAK/STAT signaling plays a pivotal role in coordinating regenerative disc growth with organismal developmental timing.
Publication Title
During Drosophila disc regeneration, JAK/STAT coordinates cell proliferation with Dilp8-mediated developmental delay.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Drosophila imaginal disc cells exhibit a remarkable ability to switch cell fates under various perturbations, a phenomenon known as transdetermination (TD). The winged eye (wge) gene induces eye-to-wing TD by its overexpression in eye imaginal discs using eye specific Gal4 driver (eyeless-Gal4). Gene network controlling this process, however, is largely unclear. Additionally, we identified that heterochromatin-related histone methyltransferase Su(var)3-9 is essential for wge-mediated TD.
Publication Title
winged eye Induces Transdetermination of Drosophila Imaginal Disc by Acting in Concert with a Histone Methyltransferase, Su(var)3-9.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- IlluminaGenomeAnalyzerIIx
Description
Glioblastomas show heterogeneous histological features. These distinct phenotypic states are thought to be associated with the presence of glioma stem cells (GSCs), which are highly tumorigenic and self-renewing sub-population of tumor cells that have different functional characteristics. To investigate gene expression including lncRNA (long non-coding RNA) in GSC, we have performed high-throughput RNA-sequencing (RNA-seq) experiment using Illumina GAIIx. Overall design: Profiles of gene expression including lncRNA in GSC were generated by RNA-seq using Illumina GAIIx.
Publication Title
Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 174 Downloadable Samples
- Illumina HiSeq 2000
Description
Oligodendrocytes (OLs) and myelin are critical for normal brain function and they have been implicated in neurodegeneration. Human neuroimaging studies have demonstrated that alterations in axons and myelin occur early in Alzheimer's Disease (AD) course. However, the molecular mechanism underlying the role of OLs in AD remains largely unknown. In this study, we systematically interrogated OL-enriched gene networks constructed from large-scale genomic, transcriptomic, and proteomic data in human AD postmortem brain samples. These robust OL networks were highly enriched for genes associated with AD risk variants, including BIN1. We corroborated the structure of the AD OL coexpression and gene-gene interaction networks through ablation of genes identified as key drivers of the networks, including UGT8, CNP, MYRF, PLP1, NPC1, and NDGR1. Perturbations of these key drivers not only caused dysregulation in their associated network neighborhoods, but also mimicked pathways of gene expression dysregulation seen in human AD postmortem brain samples. In particular, the OL subnetwork controlled by the AD risk gene PSEN1 was strongly dysregulated in AD, suggesting a potential role of PSEN1 in disrupting the myelination pathway towards the onset of AD. In summary, this study built and systematically validated the first comprehensive molecular blueprint of OL dysregulation in AD, and identified key OL- and myelination-related genes and networks as potential candidate targets for the future development of AD therapies. Overall design: The mouse knockout models have been previously described for each of Ugt8 (Coetzee et al., 1996), Cnp (Lappe-Siefke et al., 2003), and Plp1 (Klugmann et al., 1997). For each of the two conditions studied (control and homozygous knockout mice), five mice of either sex were sacrificed at postnatal day 20 and brains were flashed-frozen until analysis. The frontal cortex (FC) and cerebellum (CBM) were dissected out and individually processed. RNA was isolated using Trizol reagent and processed using Ribo-Zero rRNA removal. RNA-sequencing was performed using the Illumina HiSeq2000 with 100 nucleotide paired-end reads. RNA-sequencing reads were mapped to the mouse genome (mm10, UCSC assembly) using Bowtie (version 2.2.3.0), TopHat (version 2.0.11), and SamTools (version 0.1.19.0) using a read length of 100. Reads were converted to counts at the gene level using HTSeq on the BAM files from TopHat2 using the UCSC known genes data set.
Publication Title
Multiscale network modeling of oligodendrocytes reveals molecular components of myelin dysregulation in Alzheimer's disease.
Sample Metadata Fields
Specimen part, Subject
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
In previous in vitro study, we reported potential mechanism of cholesterol-lowering effect of Lactobacillus brevis119-2 (119-2) isolated from turnip Tsuda kabu is due to incorporation of cholesterol into 119-2 cell. In this study, we analyzed serum cholesterol and hepatic gene expression of Sprague-Dawley (SD) rat fed diet containing cholesterol with or without 119-2 for 2 weeks, to evaluate the cholesterol-lowering effect of 119-2 in vivo. Serum cholesterol of SD rat fed diet with 119-2 significantly decreased compared to SD rat fed diet without 119-2, and both viable and dead 119-2 indicated the effect. The result of hepatic gene analysis using DNA microarray suggested that potential mechanism of the cholesterol-lowering effect of 119-2 in vivo is inhibiting the activity of 3-hydroxy-3-methylglutaryl-CoA reductase by Insig (insulin induced gene) that is endoplasmic reticulum membrane protein, and catabolizing cholesterol to bile acid by Cyp7a1 (cytochrome P450 a1) that is the rate-limiting enzyme in the synthesis of bile acid from cholesterol. In addition, we concluded feeding 119-2 decreased serum low density lipoprotein (LDL) cholesterol by overexpression of Ldlr (LDL receptor gene). On the other hand, feeding Lactobacillus acidophilus ATCC43121 (ATCC) increased high density lipoprotein (HDL) cholesterol by over expression of Abca1 (ATP binding cassette sub-family A member 1 gene) and Angplt3 (Angiopoietin-like 3). These results suggested that 119-2 decrease the risk of atherosclerosis by serum cholesterol-lowering effect and improving effect of fatty liver and the LH (LDL cholesterol / HDL cholesterol) ratio.
Publication Title
Effect of Lactobacillus brevis 119-2 isolated from Tsuda kabu red turnips on cholesterol levels in cholesterol-administered rats.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Protoplasmic astrocytes in layers II to VI of the mammalian neocortex have historically been thought to comprise a homogeneous population. Given that layer-specific neuronal subtypes play essential roles in cortical circuitry, astrocytes might also be expected to support and modify this circuitry in a layer-specific manner. In order to investigate whether protoplasmic astrocytes exhibit layer-specific heterogeneity, we compared the gene expression profiles of astrocytes between upper layers (layers II to IV) and deep layers (layers V and VI). Although most genes known to be preferentially expressed in astrocytes (astrocyte-enriched genes) were equally expressed between upper-layer astrocytes and deep-layer astrocytes, some such genes (astrocyte-enriched genes or genes with known function in astrocytes) were significantly enriched in upper-layer astrocytes or deep-layer astrocytes. Overall design: With the use of fluorescence-activated cell sorting (FACS), we prepared upper-layer astrocytes and deep-layer astrocytes from the corresponding dissected layers of the somatosensory cortex of Aldh1l1-eGFP mice, in which all astrocytes are expected to be labeled with GFP. The meninges, layer I, and the corpus callosum were removed from upper- and deep-layer tissue samples. In addition, parts of layers IV and V were lost during separation of these layers in such a way as to prevent cross-contamination between the upper- and deep-layer samples. Total RNA from upper-layer astrocytes and deep-layer astrocytes (n = 3 brains from 4-week-old male mice) was isolated from sorted cells with TRIzol (Invitrogen) or RNAiso Plus (Takara) and was then subjected to reverse transcription with the use of a SMART-Seq v4 Ultra Low Input RNA Kit for Sequencing (Clontech). Bar-coded libraries were prepared with a Nextera XT DNA Library Preparation Kit (Illumina), and single-end 36-bp sequencing was performed with a HiSeq 2500 instrument (Illumina).
Publication Title
Layer-specific morphological and molecular differences in neocortical astrocytes and their dependence on neuronal layers.
Sample Metadata Fields
Specimen part, Subject
View Samples