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GSE34224
Mus musculus
16 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
The MYB oncogene is widely expressed in acute leukemias and is important for the continued proliferation of leukemia cells, raising the possibility that MYB may be a therapeutic target. However realization of this potential requires (i) a significant therapeutic window for MYB inhibition, given its essential role in normal hematopoiesis; and (ii) an approach for developing an effective therapeutic. We previously showed that the interaction of Myb with the coactivator CBP/p300 is essential for its transforming activity. Here we use hematopoietic cells from the Booreana mouse strain, which carries a mutation in Myb that prevents interaction with CBP/p300, to examine the requirement for this interaction in myeloid transformation and leukemogenesis. Using this strain and a strain (plt6) carrying a complementary mutation in p300, we show that the Myb-p300 interaction is essential for in vitro transformation by the myeloid leukemia oncogenes AML1-ETO, AML1-ETO9a, MLL-ENL, and MLL-AF9. We further show that unlike cells from wild-type (WT) mice, Booreana cells fail to induce leukemia upon transplantation into irradiated recipients following transduction with an AML1-ETO9a retrovirus. These data highlight disruption of the Myb-p300 interaction as a potential therapeutic strategy for AML and suggest that such a strategy would have a useable therapeutic index since Booreana mice, unlike Myb null mice, are viable. Finally we have begun to explore the molecular basis of the these observations by gene expression profiling; this highlighted several genes previously implicated in myeloid leukemogenesis as being differentially expressed between WT and Booreana cells transduced with AML1-ETO9a.
Publication Title
Interaction of c-Myb with p300 is required for the induction of acute myeloid leukemia (AML) by human AML oncogenes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 26 Downloadable Samples
Illumina HiSeq 2000
Description
RNA editing is a mutational mechanism that specifically alters the nucleotide content in sets of transcripts while leaving their cognate genomic blueprint intact. Editing has been detected from bulk RNA-seq data in thousands of distinct transcripts, but apparent editing rates can vary widely (from under 1% to almost 100%). These observed editing rates could result from approximately equal rates of editing within each individual cell in the bulk sample, or alternatively, editing estimates from a population of cells could reflect an average of distinct, biologically significant editing signatures that vary substantially between individual cells in the population. To distinguish between these two possibilities we have constructed a hierarchical Bayesian model which quantifies the variance of editing rates at specific sites using RNA-seq data from both single cells and a cognate bulk sample consisting of ~ 106 cells. The model was applied to data from murine bone-marrow derived macrophages and dendritic cells, and predicted high variance for specific edited sites in both cell types tested. We then 1 validated these predictions using targeted amplification of specific editable transcripts from individual macrophages. Our data demonstrate substantial variance in editing signatures between single cells, supporting the notion that RNA editing generates diversity within cellular populations. Such editing-mediated RNA-level sequence diversity could contribute to the functional heterogeneity apparent in cells of the innate immune system. Overall design: 26 samples were subjected to RNA-seq: 24 single WT macrophages, and 2 bulk samples (Apobec1 WT and KO macrophages), consisting of 500,000-1 million cells each.
Publication Title
RNA editing generates cellular subsets with diverse sequence within populations.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 19 Downloadable Samples
- Illumina HiSeq 2000
Description
We ovexpressed human alpha synuclein alone or together with Nurr1 in mouse primary midbrain cultures and identified the full spectrum of genes whose expression is affected by alpha synuclein, including genes whose expression is normalized after Nurr1 overexpression. Moreover we treated mouse primary midbrain cultures with Bexarotene or short hairpin RNA fro Nurr1, sorted out the dopamine neurons and assessed the effects of Bexarotene and of the Nurr1 downregulation on gene expression. Overall design: Comparison of 3 Synuclein samples to 5 controls (RFP), Comparison of 3 Synuclein + Nurr1 samples to 5 controls (RFP), Comparison of 3 Bexarotene samples to 3 controls (DMSO), comparison of 1 short hairpin against Nurr1 to 1 control (scrambled).
Publication Title
Nurr1 and Retinoid X Receptor Ligands Stimulate Ret Signaling in Dopamine Neurons and Can Alleviate α-Synuclein Disrupted Gene Expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Homeostatic hematopoietice stem cells (HSCs) with greater divisional history lose repopulating potential after very few cell divisions. Divisional history overrides both phenotype and immediate quiescence in determining functional activity. In GFP label retaining system GFP is progressively diluted when cells proceed through a cascade of divisions.
Publication Title
Divisional history and hematopoietic stem cell function during homeostasis.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 9 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Assessment of the putative differential gene expression profiles in high osmolality-treated bovine nucleus pulposus intervertebral disc cells for a short (5 h) and a long (24 h) time period. Identification of novel genes up- or down-regulated as an early or a late response to hyperosmotic stress.
Publication Title
Deficiency in the α1 subunit of Na+/K+-ATPase enhances the anti-proliferative effect of high osmolality in nucleus pulposus intervertebral disc cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 25 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The metabolic syndrome (MetS) is characterized by the presence of metabolic abnormalities that include abdominal obesity, dyslipidemia, hypertension, increased blood glucose/insulin resistance, hypertriglyceridemia and increased risk for cardiovascular disease (CVD). The ApoE*3Leiden.human Cholesteryl Ester Transfer Protein (ApoE3L.CETP) mouse model manifests several features of the MetS upon high fat diet (HFD) feeding. Moreover, the physiological changes in the white adipose tissue (WAT) contribute to MetS comorbidities. The aim of this study was to identify transcriptomic signatures in the gonadal WAT of ApoE3L.CETP mice in discrete stages of diet-induced MetS.
Publication Title
Transcriptome analysis of the adipose tissue in a mouse model of metabolic syndrome identifies gene signatures related to disease pathogenesis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
We generated de novo induced pluripotent stem cells (iPSCs) from two Parkinson’s Disease patients (PD) harboring the p.A53T mutation. iPSC-derived mutant neurons displayed disease-relevant phenotypes at basal conditions, including protein aggregation, compromised neuritic outgrowth and contorted axons with swollen varicosities containing aSyn and tau. We have performed RNA Sequencing (RNA-Seq) of neurons from PD patient and control samples. RNA sequencing has also been performed to neurons derived from HUES samples subjected to the same differentiation protocol as reference. Overall design: We have performed RNA Sequencing (RNA-Seq) in neurons PD and control samples (two clones from each individual), along with HUES-derived neurons.
Publication Title
Defective synaptic connectivity and axonal neuropathology in a human iPSC-based model of familial Parkinson's disease.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 251 Downloadable Samples
- IlluminaHiSeq2000
Description
Definitive hematopoiesis emerges via an endothelial-to-hematopoietic transition in the aorta-gonad-mesonephros (AGM) region and placenta. We have recently demonstrated the induction of hematopoietic stem/progenitors (HSPCs) from mouse fibroblasts with a combination of transcription factors progressing through endothelial-like precursors. Here, guided by our in vitro programming experiments we analyzed mouse placentas for the presence of the precursor phenotype. We identified a small population of CD34+ Sca1+Prom1+ (34PS) cells in mid-gestation placentas that do not express the pan-hematopoietic marker CD45. After isolation and culture 34PS cells acquire CD45 and generate large hematopoietic as well as cobblestone colonies. Prom1+ cells localize to the placental vascular labyrinth where HSPCs emerge. 34PS cells express markers associated with the hemogenic endothelium (CD31, Tie2, VE-Cadherin, Sox17, Runx1, Scl) and also markers identified by direct induction (Itga6/CD49f). This population is heterogeneous for the early hematopoietic marker CD41 and expresses the programming transcription factors. Remarkably, global gene expression profiles of placental 34PS cells correlate with AGM-derived hemogenic endothelium and fibroblast-derived precursors. Finally, when co-cultured with stroma placental 34PS cells give rise to B/T lymphoid cells as well as mixed colonies containing erythroid, myeloid and megakaryocytic cell lineages. In summary, we show that direct in vitro conversion provided a cell surface phenotype for the isolation of hemogenic precursors in vivo. Our findings provide insights into the specification of definitive hemogenesis in the placenta, in depth characterization of hemogenic precursor populations and the first evidence that direct in vitro conversion approaches can be used as a valuable tool to address basic developmental questions in vivo. Overall design: mRNAseq profiling on populations isolated by selected marker fluorescence activated cell sorting The 'E10_E12_HSPC_SingleCell_FPKM.txt.gz' contains the processed data for GSM1890353-GSM1890496.
Publication Title
Hematopoietic Reprogramming In Vitro Informs In Vivo Identification of Hemogenic Precursors to Definitive Hematopoietic Stem Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Definitive hematopoiesis emerges during embryogenesis via an endothelial-to-hematopoietic transition. We attempted to induce this process in mouse fibroblasts by screening a panel of factors for hemogenic activity. We identified a combination of four transcription factors, Gata2, Gfi1b, cFos, and Etv6 that efficiently induces endothelial-like precursor cells with the subsequent appearance of hematopoietic cells. The precursor cells express a human CD34 reporter, Sca1 and Prominin1 within a global endothelial transcription program. Emergent hematopoietic cells possess nascent/specifying hematopoietic stem cell gene expression profiles and cell surface phenotypes. After transgene silencing and reaggregation culture, the specified cells generate hematopoietic colonies in vitro. Thus, we have shown that a simple combination of transcription factors is sufficient to induce a complex, dynamic and multi-step developmental program in vitro. These findings provide insights into the specification of definitive hemogenesis and a platform for future development of patient-specific stem/progenitor cells as well as more differentiated blood products. Overall design: mRNA-seq profiling on populations generated after transduction with Gata2, Gfi1b, cFos and Etv6 at day 20 and day 35.
Publication Title
Induction of a hemogenic program in mouse fibroblasts.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Mus musculus
- 7 Downloadable Samples
- Illumina HiSeq 2000
Description
We have ablated TAF10 in the erythroid compartment only by crossing the TAF10lox mice with the EpoR-Cre mice and we have studied the development of the erythroid cells in vivo. TAF10 ablation led to embryonic death at E13.5 while at E12.5 there was a clear developmental defect which was reflected in the transcriptional profile of the fetal liver cells. Gata1-target genes were mostly affected and were responsible for the lethal phenotype. Overall design: mRNA from E12.5 fetal livers of TAF10lox/KO:EpoR-Cre+/- (TAF10KO) mice, TAF10HET and WT mice was profiled by NGS (Illumina).
Publication Title
TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse Erythropoiesis.
Sample Metadata Fields
No sample metadata fields
View Samples