GM-CSF signaling was previously reported to have a negative effect on a murine model of (8;21)-induced leukemia. Gene expression profiling of MigR1 (Mig) control and RUNX1-ETO (RE), the oncofusion protein generated from t(8;21), murine Lin-/c-Kit+ hematopoietic stem/progenitor cells (HSPCs) was conducted to further elucidate the mechanisms mediating the negative effect induced by GM-CSF signaling in t(8;21) cells,
Restoration of MYC-repressed targets mediates the negative effects of GM-CSF on RUNX1-ETO leukemogenicity.
Specimen part, Treatment
View SamplesWe examined the microRNAs (miRNAs) expressed in chronic lymphocytic leukemia (CLL) and identified miR-150 as the most abundant, but with leukemia-cell-expression levels that varied among patients. CLL cells that expressed ZAP-70 or that used unmutated IGHV each had a median expression-level of miR-150 that was significantly lower than that of ZAP-70-negative CLL cells or those that used mutated IGHV. In samples stratified for expression of miR-150, CLL cells with low-level miR-150 expressed relatively higher levels of forkhead box P1 (FOXP1) and GRB2-associated binding protein 1 (GAB1), genes with 3 UTRs having evolutionary-conserved binding sites for miR-150. High-level expression of miR-150 could repress expression of these genes, which encode proteins that may enhance B-cell receptor (BCR) signaling, a putative CLL-growth/survival signal. Also, high-level expression of miR-150 levels was a significant independent predictor of longer treatment-free-survival (TFS) or overall survival (OS), whereas an inverse association was observed for high-level expression of GAB1 or FOXP1 for OS. This study demonstrates that expression of miR-150 can influence the relative expression of GAB1 and FOXP1 and the signaling potential of the B-cell receptor (BCR), thereby possibly accounting for the noted association of expression of miR-150 and disease outcome.
miR-150 influences B-cell receptor signaling in chronic lymphocytic leukemia by regulating expression of GAB1 and FOXP1.
Specimen part, Disease stage
View SamplesThe purpose of this study was to identify putative downstream targets of the transcription factor ZIC2 in the mouse embryo. The results indicate loss of NODAL pathway expression, consistent with the observed phenotype of right isomerism in heart, lungs and viscera.
A Requirement for Zic2 in the Regulation of Nodal Expression Underlies the Establishment of Left-Sided Identity.
Specimen part
View SamplesOxidized phospoholipids are a pro-inflammatory component of minimally modified lipoproteins that get trapped in the subendothelial space of atherosclerotic plaques of large arteries. To model the response of endothelial cells in a pro-atherosclerotic enviroment we measured the expression in primary endothelial cells with and without treatment with oxidized phsopolipids from 96 genetically identical donors of anonymous origin.
Network for activation of human endothelial cells by oxidized phospholipids: a critical role of heme oxygenase 1.
Sex, Subject
View SamplesOxidized phospoholipids are a pro-inflammatory component of minimally modified lipoproteins that get trapped in the subendothelial space of atherosclerotic plaques of large arteries. To model the response of endothelial cells in a pro-atherosclerotic enviroment we measured the expression in primary endothelial cells with and without treatment with oxidized phsopolipids from 96 genetically identical donors of anonymous origin.
Systems genetics analysis of gene-by-environment interactions in human cells.
Sex, Subject
View SamplesCellular and tissue defects associated with insulin resistance are coincident with transcriptional abnormalities and are improved after insulin sensitization with thiazolidinedione (TZD) PPAR ligands.
Mechanisms of human insulin resistance and thiazolidinedione-mediated insulin sensitization.
Specimen part, Subject
View SamplesTo understand the molecular mechanisms of human lung macrophage development, function, and role in BPD pathogenesis, we conducted a clinical study using isolated tracheal aspirate macrophages from intubated preterm infants born before 30 wk gestation. One hundred twenty-eight patients intubated for respiratory distress syndrome and surfactant administration were consented for the study.
Transcriptional profiling of lung macrophages identifies a predictive signature for inflammatory lung disease in preterm infants.
Sex, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Increased risk of genetic and epigenetic instability in human embryonic stem cells associated with specific culture conditions.
Sex, Specimen part, Cell line
View SamplesThe self-renewal and differentiation capacities of human pluripotent stem cells (hPSCs) make them good sources of cells for cell transplantation therapy, drug development, and studies of cellular differentiation and development. However, the large numbers of cells necessary for many of these applications require extensive expansion of hPSC cultures, a process that has been associated with applications require extensive expansion of hPSC cultures, a process that has been associated with genetic and epigenetic alterations. We have performed a systematic study over more than 100continuous passages to identify characteristics of culture conditions (including passage method, substrate, and media type) that influence the genetic and epigenetic stability and the phenotypic characteristics of hPSCs. The predominant effects we observed were increased genetic instability with enzymatic passage, higher cell proliferation with feeder-free substrate, and variations among cultures in global gene expression and DNA methylation with time in culture. We observed recurrent duplications in two genomic regions that have been noted in earlier studies to be hotspots for duplication in hPSCs, as well as a previously unreported recurrent deletion of the tumor suppressor gene TP53 in all but one of the long-term culture conditions; the exception was the condition using mechanical passaging on feeder layers. The deletion of TP53 is associated with decreased mRNA expression of TP53, as well as alterations in the expression of several other genes in the TP53 pathway, which taken together indicate a decrease in the function of the TP53 pathway. Our results highlight the need for careful assessment of effects of culture conditions on cells intended for clinical therapies.
Increased risk of genetic and epigenetic instability in human embryonic stem cells associated with specific culture conditions.
Sex, Cell line
View SamplesThe disrupted genetic mechanisms underlying neural abnormalities in Autism Spectrum Disorder remain mostly unknown and speculative. No biological marker nor genetic signature is currently available to assist with early diagnosis.
Prediction of autism by translation and immune/inflammation coexpressed genes in toddlers from pediatric community practices.
Sex, Specimen part
View Samples