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GSE33808
Mus musculus
4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The polycomb group (PcG) proteins function in gene silencing through histone modifications. They form chromatin-associated multiprotein complexes, termed polycomb repressive complex (PRC) 1 and PRC2. These two complexes work in a coordinated manner in the maintenance of cellular memories through transcriptional repression of target genes. EZH2 is a catalytic component of PRC2 and trimethylates histone H3 at lysine 27 to transcriptionally repress the target genes. PcG proteins have been characterized as general regulators of stem cells, but recent works also unveiled their critical roles in cancer.
Publication Title
Ezh2 augments leukemogenicity by reinforcing differentiation blockage in acute myeloid leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 1000
Description
Hypoxia inducible factor-1a (HIF-1a) is a critical transcription factor for the hypoxic response, angiogenesis, normal hematopoietic stem cell regulation, and cancer development. Importantly, HIF-1a is also a key regulator for immune cell activation. In order to determine whether HIF-1a is sufficient for developing MDS phenotypes, we generated blood specific inducible HIF-1a transgenic mice. Using Vav1-Cre/Rosa26-loxP-Stop-loxP (LSL) rtTA driver, stable HIF-1a can be induced in a doxycycline administration dependent manner. After induction, HIF-1a-induced mice developed thrombocytopenia, leukocytopenia, macrocytic anemia, and multi-lineage dysplasia. We also found activation of both innate and adaptive immunity in HIF-1a- induced mice compared to those from control mice. Taken together, these data suggest that HIF-1a is sufficient to trigger a variety of key MDS features Overall design: Expression profiles of mRNA in HSPCs from constitutively active form of HIF1a protein induced mice and their control mice.
Publication Title
Pathobiological Pseudohypoxia as a Putative Mechanism Underlying Myelodysplastic Syndromes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 1000
Description
The MLL-PTD mutation is found in patients with MDS and AML, and not in other hematological malignancies. Previously, we showed that Mll-PTD knock-in heterozygous mice (MllPTD/WT mice) present with several MDS-associated features. However, these phenotypes are insufficient to constitute bona fide MDS. MllPTD/WT mice do not generate MDS or AML in primary or transplant recipient mice. This suggests that additional genetic and/or epigenetic defects are necessary for transformation to MDS or AML. In secondary AML and de novo AML, MLL-PTD mutation is significantly associated with mutations in RUNX1 and with the FLT3-ITD mutations. In fact, the combination of MLL-PTD with the FLT3-ITD allele leads to AML in mice. We combined the MLL-PTD with RUNX1 mutant proteins, in order to generate a new mouse model for MDS. We generated MllPTD/WT/Runx1Flox/Flox/Mx1-Cre mice to model loss-of-function RUNX1 mutations. To test the significance of HIF-1a in this model, we also generated MllPTD/WT/Runx1Flox/Flox/Hif-1aFlox/Flox/Mx1-Cre mice and genetically eliminated Hif-1a expression. We analyzed gene expression variations in the HSPCs comparing the MllPTD/WT/Runx1?/? with or without HIF-1a abrogation. Overall design: Expression profiles of mRNA in HSPCs from MLL-PTD/Runx1-KO mice with or without HIF-1a
Publication Title
Pathobiological Pseudohypoxia as a Putative Mechanism Underlying Myelodysplastic Syndromes.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 78 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To identify molecular pathological alterations in AD brains, we performed interspecies comparative microarray analyses using RNAs prepared from postmortem human brain tissues donated for the Hisayama study and hippocampal RNAs from the triple-transgenic mouse model of AD (3xTg-AD)
Publication Title
Altered expression of diabetes-related genes in Alzheimer's disease brains: the Hisayama study.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To identify molecular pathological alterations in AD brains, we performed interspecies comparative microarray analyses using RNAs prepared from postmortem human brain tissues donated for the Hisayama study and hippocampal RNAs from the triple-transgenic mouse model of AD (3xTg-AD)
Publication Title
Altered expression of diabetes-related genes in Alzheimer's disease brains: the Hisayama study.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
GeneChip-based screen for genes induced in the initial phase of neural differentiation from ES cells.
Publication Title
Intrinsic transition of embryonic stem-cell differentiation into neural progenitors.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Regulation of organ size is important for development and tissue homeostasis. In Drosophila, Hippo signaling controls organ size by regulating the activity of a TEAD transcription factor, Scalloped, through modulation of its coactivator protein Yki. The role of mammalian Tead proteins in growth regulation, however, remains unknown. Here we examined the role of mouse Tead proteins in growth regulation. In NIH3T3 cells, cell density and Hippo signaling regulated the activity of Tead proteins by modulating nuclear localization of a Yki homologue, Yap, and the resulting change in Tead activity altered cell proliferation. Tead2-VP16 mimicked Yap overexpression, including increased cell proliferation, reduced cell death, promotion of EMT, lack of cell contact inhibition, and promotion of tumor formation. Growth promoting activities of various Yap mutants correlated with their Tead-coactivator activities. Tead2-VP16 and Yap regulated largely overlapping sets of genes. However, only a few of the Tead/Yapregulated genes in NIH3T3 cells were affected in Tead1-/-;Tead2-/- or Yap-/- embryos. Most of the previously identified Yap-regulated genes were not affected in NIH3T3 cells or mutant mice. In embryos, levels of nuclear Yap and Tead1 varied depending on cell types. Strong nuclear accumulation of Yap and Tead1 were seen in myocardium, correlating with requirements of Tead1 for proliferation. However, their distribution did not always correlate with proliferation. Taken together, mammalian Tead proteins regulate cell proliferation and contact inhibition as a transcriptional mediator of Hippo signaling, but the mechanisms by which Tead/Yap regulate cell proliferation differ depending on cell types, and Tead, Yap and Hippo signaling may play multiple roles in mouse embryos.
Publication Title
Mammalian Tead proteins regulate cell proliferation and contact inhibition as transcriptional mediators of Hippo signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We found that a H3K4 specific histone methyltransferase MLL1, a mammalian homologue of Drosophila trithorax, is essential for circadian transcription. MLL1 is in a complex with CLOCK:BMAL1 and contributes to their rhythmic recruitment to circadian promoters and cyclic H3K4 tri-metylation. To analyze the function of MLL1 on circadian gene regulation, we performed comparative microarray analysis of global gene expression levels in WT and MLL1-deficient MEF, at two different circadian time points (CT18 and CT30). This analysis identified several genes whose expression levels were remarkably changed between CT18 and CT30 in WT and MLL1-KO MEF. Typical clock-regulated genes such as Per2, Per3, Bmal1, or Dbp were found to be changing in WT but not in MLL1-KO MEFs.
Publication Title
The histone methyltransferase MLL1 permits the oscillation of circadian gene expression.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq1500
Description
Human embryonic stem cells (hESCs) have the unique property of immortality, ability to infinitely self-renew and survive in vitro. In contrast to tumor-deribed cells, their immortality are free from any genomic abberations. Instead, they depend on the AKAP-Lbc/Rho signaling cascade. To understand the downstream way, we performed RNA-seq analyses between normal and AKAP-Lbc-depleted hESCs using the doxycyclin-inducible gene silensing strategy. Overall design: We use the genetically modified hESCs in which AKAP-13-targeting shRNA is induced by doxycyclin(dox) treatment. To minimize cell loss during treatment, anti-apoptotic factor Bcl-XL is overexpressed. We collected RNA from dox-treated and untreated cells in biological triplicate. We measured gene expression in these 2 sample groups using RNA-seq (illumina HiSeq) .
Publication Title
Rho-Signaling-Directed YAP/TAZ Activity Underlies the Long-Term Survival and Expansion of Human Embryonic Stem Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Genome instability is a potential limitation to the research and therapeutic application of induced pluripotent stem cells (iPSCs). Observed genomic variations reflect the combined activities of DNA damage, cellular DNA damage response (DDR), and selection pressure in culture. To understand the contribution of DDR on the distribution of copy number variations (CNVs) in iPSCs, we mapped CNVs of iPSCs with mutations in the central DDR gene ATM onto genome organization landscapes defined by genome-wide replication timing profiles. We show that following reprogramming the early and late replicating genome is differentially affected by CNVs in ATM deficient iPSCs relative to wild type iPSCs. Specifically, the early replicating regions had increased CNV losses during retroviral reprogramming. This differential CNV distribution was not present after later passage or after episomal reprogramming. Comparison of different reprogramming methods in the setting of defective DNA damage response reveals unique vulnerability of early replicating open chromatin to retroviral vectors.
Publication Title
Influence of ATM-Mediated DNA Damage Response on Genomic Variation in Human Induced Pluripotent Stem Cells.
Sample Metadata Fields
Specimen part
View Samples