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GSE45194
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Pre-leukemic mutations are thought to promote clonal expansion of hematopoietic stem cells (HSCs) by increasing self-renewal and competitiveness. However, mutations that increase HSC proliferation tend to reduce competitiveness and self-renewal potential, raising the question of how a mutant HSC can sustainably outcompete wild-type HSCs. Activating mutations in NRAS are prevalent in human myeloproliferative disease and leukemia. Here we show that a single allele of oncogenic NrasG12D increases HSC proliferation but also increases reconstituting and self-renewal potential upon serial transplantation in irradiated mice, all without immortalizing HSCs or causing leukemia in our experiments. NrasG12D also confers long-term self-renewal potential upon multipotent progenitors. To explore the mechanism by which NrasG12D promotes HSC proliferation and self-renewal we assessed HSC cell cycle kinetics using H2B-GFP label retention. We found that NrasG12D had a bimodal effect on HSCs, increasing the proliferation of some HSCs while increasing the quiescence and competitiveness of other HSCs. One signal can therefore increase HSC proliferation, competitiveness, and self-renewal through a bimodal effect that promotes proliferation in some HSCs and quiescence in others.
Publication Title
Oncogenic Nras has bimodal effects on stem cells that sustainably increase competitiveness.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Affymetrix Mouse Promoter 1.0R Array (mmprompr)
Description
Expression microarrays were employed to identify genes induced by phorbol ester and ionomycin stimulation of EL4 cells. EL4 is a murine T cell line. To identify induced genes that were independent of new protein synthesis cells were pre-treated with cycloheximide. This expression study was used in conjunction with histone acetylation ChIP-chip to determine if inducible genes had a specific histone acetylation profile and whether the acetylation profile differed for genes with different kinetics of induction.
Publication Title
Defining the chromatin signature of inducible genes in T cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
IlluminaGenomeAnalyzerIIx
Description
Multidrug resistance (MDR) frequently develops in cancer patients exposed to chemotherapeutic agents and is usually brought about by over-expression of P-glycoprotein (P-gp) which acts as a drug efflux pump. MiRNAome profiling using next-generation sequencing identified differentially expressed microRNAs (miRs) between parental K562 cells and MDR K562 cells (K562/ADM) induced by chronic adriamycin treatment. Overall design: MiRNAome profiling in untreated K562 cells and K562 cells exposed to long-term adriamycin treatment
Publication Title
Changes in the expression of miR-381 and miR-495 are inversely associated with the expression of the MDR1 gene and development of multi-drug resistance.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Gene expression was evaluated in 9 appendix samples removed from patients who went to the operating room with the diagnosis of acute appendicitis and 4 samples removed for non-inflammatory reasons.
Publication Title
Acute appendicitis is characterized by a uniform and highly selective pattern of inflammatory gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Acute cardiac allograft rejection is a serious complication of heart transplantation. Investigating molecular processes in whole blood via microarrays is a promising avenue of research in transplantation, particularly due to the non-invasive nature of blood sampling. However, whole blood is a complex tissue and the consequent heterogeneity in composition amongst samples is ignored in traditional microarray analysis. This complicates the biological interpretation of microarray data. Here we have applied a statistical deconvolution approach, cell-specific significance analysis of microarrays (csSAM), to whole blood samples from subjects either undergoing acute heart allograft rejection (AR) or not (NR). We identified eight differentially expressed probe-sets significantly correlated to monocytes (mapping to 6 genes, all down-regulated in ARs versus NRs) at a false discovery rate (FDR) <= 15%. None of the genes identified are present in a biomarker panel of acute heart rejection previously published by our group and discovered in the same data.
Publication Title
White blood cell differentials enrich whole blood expression data in the context of acute cardiac allograft rejection.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 108 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Contemporary treatment of pediatric acute myeloid leukemia (AML) requires the assignment of patients to specific risk groups. To explore whether expression profiling of leukemic blasts could accurately distinguish between the known risk groups of AML, we analyzed 130 pediatric and 20 adult AML diagnostic bone marrow or peripheral blood samples using the Affymetrix U133A microarray. Class discriminating genes were identified for each of the major prognostic subtypes of pediatric AML, including t(15;17)[PML-RARalpha], t(8;21)[AML1-ETO], inv(16) [CBFbeta-MYH11], MLL chimeric fusion genes, and cases classified as FAB-M7. When subsets of these genes were used in supervised learning algorithms, an overall classification accuracy of more than 93% was achieved. Moreover, we were able to use the expression signatures generated from the pediatric samples to accurately classify adult de novo AMLs with the same genetic lesions. The class discriminating genes also provided novel insights into the molecular pathobiology of these leukemias. Finally, using a combined pediatric data set of 130 AMLs and 137 acute lymphoblastic leukemias, we identified an expression signature for cases with MLL chimeric fusion genes irrespective of lineage. Surprisingly, AMLs containing partial tandem duplications of MLL failed to cluster with MLL chimeric fusion gene cases, suggesting a significant difference in their underlying mechanism of transformation. All the gene expression arrays are available through http://www.stjuderesearch.org/site/data/AML1/ in the original study (PMID:15226186). To study the RAS gene expression in the human AML patients, a total of 104 AML cases with known KRAS and NRAS status (including 72 gene expression arrays in the original study and 32 additional arrays acquired later on), as well as 4 CD34+ normal bone marrow cases deposited in GEO GSE33315, were including in this depository.
Publication Title
Dominant role of oncogene dosage and absence of tumor suppressor activity in Nras-driven hematopoietic transformation.
Sample Metadata Fields
Disease, Disease stage
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The oncogenic proteins expressed in human cancer cells are exceedingly difficult targets for drug discovery due to intrinsic properties of the Ras GTPase switch. As a result, recent efforts have largely focused on inhibiting Ras-regulated kinase effector cascades, particularly the Raf/MEK/ERK and PI3 kinase/Akt/mTOR pathways. We constructed murine stem cell leukemia virus (MSCV) vectors encoding oncogenic K-RasD12 with additional second site amino acid substitutions that that impair PI3 kinase/Akt or Raf/MEK/ERK activation and performed bone marrow transduction/transplantation experiments in mice. In spite of attenuated signaling properties, defective K-Ras oncoproteins induced aggressive clonal T lineage acute lymphoblastic leukemia (T-ALL). These leukemias exhibited a high frequency of somatic Notch1 mutations, which is also true of human T-ALL. Multiple independent T-ALLs restored full oncogenic Ras activity by acquiring third site mutations within the viral KrasD12 transgenes. Other leukemias with undetectable PTEN and elevated phosphoryated Akt levels showed a similar gene expression profile to human early T progenitor (ETP) T-ALL. Expressing oncoproteins that are defective for specific functions is a general strategy for assessing requirements for tumor maintenance and uncovering potential mechanisms of drug resistance in vivo. In addition, our observation that defective Kras oncogenes regain potent cancer initiating activity strongly supports simultaneously targeting distinct components of Ras signaling networks in the substantial fraction of cancers with RAS mutations.
Publication Title
Defective K-Ras oncoproteins overcome impaired effector activation to initiate leukemia in vivo.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2500, Illumina HiSeq 2000
Description
Relatively little is known about how the identity of early neuronal stem cells changes before and after neural tube closure (neurulation). We performed RNA sequencing on microdissected forebrain precursors and revealed sharp reductions in expresion of protein biosynthetic machinery after neurulation. These reductions were paralleled by down-regulation of Myc, which regulated forebrain precursor ribosome ribosome biogenesis. To study consequences of Myc dysregulation, we overexpressed Myc in Nestin+ neural progenitors, sorted these progenitors for RNA sequencing, and identified 135 genes that are differentially expressed between Myc-overexpressed embryos and their wildtype littermates. Overall design: The first RNA sequencing dataset contains micordissected neuroepithelium from E8.5 and E10.5 mouse embryos, two biological replicates for each age. The second RNA sequencing dataset contain FACS isolated Pax6+ neural progenitors form the cortex of E13.5 MYC-overexpressed embryos and their wildtype littermates, three biological replicates for each genotype.
Publication Title
Downregulation of ribosome biogenesis during early forebrain development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Low back pain (LBP) is one of the most prevalent conditions which need medical advice and result in chronic disabilities. Degenerative disc disease (DDD) is a common reason for LBP. A lot of researchers think that CEP degeneration play critical roles in the initiation and development of DDD. In recent years, researchers have put interests on cell-based therapies for regenerating disc structure and function. Our research team has isolated cartilage endplate-derived stem cells (CESCs) and validated their chondrogenic and osteogenic differentiation ability. Enhanced chondrogenic differentiation and inhibited osteogenic differentiation of CESCs may retard CEP calcification and restore the nutrition supply, possibly regenerating the degenerated discs.
Publication Title
Global Gene Expression Profiling and Alternative Splicing Events during the Chondrogenic Differentiation of Human Cartilage Endplate-Derived Stem Cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Flow sorted mouse LNEP cells isolated from normal lungs and influenza-infected lungs (day 17 PR8) Overall design: Highly purified quiescent LNEPs (EpCAMposb4posCC10negFoxJ1neg) and activated LNEPs (Krt5-CreERT2 traced cells 17 days post infection) were flow sorted and extracted for RNA using ReliaPrepâ„¢ RNA Tissue Miniprep kit (Promega).
Publication Title
Local lung hypoxia determines epithelial fate decisions during alveolar regeneration.
Sample Metadata Fields
Specimen part, Subject
View Samples