Background: Gene expression profiling has shown its ability to identify with high accuracy low cytogenetic risk acute myeloid leukemia such as acute promyelocytic leukemia and leukemias with t(8;21) or inv(16). The aim of this gene expression profiling study was to evaluate to what extent suboptimal samples with low leukemic blast load (range, 2-59%) and/or poor quality control criteria could also be correctly identified. Methods: Specific signatures were first defined so that all 71 acute promyelocytic leukemia, leukemia with t(8;21) or inv(16)-AML as well as cytogenetically normal acute myeloid leukemia samples with at least 60% blasts and good quality control criteria were correctly classified (training set). The classifiers were then evaluated for their ability to assign to the expected class 111 samples considered as suboptimal because of a low leukemic blast load (n=101) and/or poor quality control criteria (n=10) (test set). Results: With 10-marker classifiers, all training set samples as well as 97 of the 101 test samples with a low blast load, and all 10 samples with poor quality control criteria were correctly classified. Regarding test set samples, the overall error rate of the class prediction was below 4 percent, even though the leukemic blast load was as low as 2%. Sensitivity, specificity, negative and positive predictive values of the class assignments ranged from 91% to 100%. Of note, for acute promyelocytic leukemia and leukemias with t(8;21) or inv(16), the confidence level of the class assignment was influenced by the leukemic blast load. Conclusion: Gene expression profiling and a supervised method requiring 10-marker classifiers enable the identification of favorable cytogenetic risk acute myeloid leukemia even when samples contain low leukemic blast loads or display poor quality control criterion.
Routine use of microarray-based gene expression profiling to identify patients with low cytogenetic risk acute myeloid leukemia: accurate results can be obtained even with suboptimal samples.
Time
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Routine use of microarray-based gene expression profiling to identify patients with low cytogenetic risk acute myeloid leukemia: accurate results can be obtained even with suboptimal samples.
Specimen part, Time
View SamplesWe have previously identified hundreds of human islet lncRNAs. Here we functionally characterise 12 such lncRNAs in EndoC-betaH1 cells through loss of function studies.
Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks.
Cell line
View SamplesTumour hypoxia exhibits a highly dynamic spatial and temporal distribution and is associated with increased malignancy and poor prognosis.
Two phases of disulfide bond formation have differing requirements for oxygen.
Treatment
View SamplesTMPRSS6 is a type II transmembrane serine protease and is revealed by our work to be part of a low-iron sensing pathway. When animal gets iron deficient, TMPRSS6 is required to shut off hepcidin gene, so as to allow iron to be uptaken from GI tract. The mutant mouse, which was generated by ENU mutagenesis, has developed microcytic anemia. The phenotype is caused by a splicing error in Tmprss6 gene. However, the mechanism of TMPRSS6 effect remains elusive. To gain further insight into the molecular components of the TMPRSS6 signaling pathway, we overexpressed either TMPRSS6 or its mutant version of protein in human liver carcinoma cell line HepG2 cells, and compared the transcription status betweem these two treatments.
The serine protease TMPRSS6 is required to sense iron deficiency.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Hypoxia increases genome-wide bivalent epigenetic marking by specific gain of H3K27me3.
Cell line, Time
View SamplesPurpose: Study hypoxia and reoxygenation induced changes in genome-wide gene expression
Quantitative analysis of ChIP-seq data uncovers dynamic and sustained H3K4me3 and H3K27me3 modulation in cancer cells under hypoxia.
Cell line, Time
View SamplesMicroglia colonize the brain parenchyma at early stages of development and accumulate in specific regions where they actively participate in cell death, angiogenesis, neurogenesis and synapse elimination. A recurring feature of embryonic microglial distribution is their association with developing axon tracts which, together with in vitro data, supports the idea of a physiological role for microglia in neurite development. Yet the demonstration of this role of microglia is still lacking. Here, we have studied the consequences of microglial dysfunction on the formation of the corpus callosum, the largest connective structure in the mammalian brain, which shows consistent microglial accumulation during development. We studied two models of microglial dysfunction: the loss-of-function of DAP12, a key microglial-specific signaling molecule, and a model of maternal inflammation by peritoneal injection of LPS at E15.5. We performed transcriptional profiling of maternally inflamed and Dap12-mutant microglia at E17.5. We found that both treatments principally down-regulated genes involved in nervous system development and function, particularly in neurite formation. We then analyzed the functional consequences of these microglial dysfunctions on the formation of the corpus callosum. We also took advantage of the Pu.1-/- mouse line, which is devoid of microglia. We now show that all three models of altered microglial activity resulted in the same defasciculation phenotype. Our study demonstrates that microglia are actively involved in the fasciculation of corpus callosum axons.
Microglia shape corpus callosum axon tract fasciculation: functional impact of prenatal inflammation.
Sex, Specimen part, Treatment
View SamplesHuman conjunctival cell lines are useful tools for modeling ocular surface disease and evaluation of ocular drugs. Here we demonstrate that the IOBA-NHC and the ChWK conjunctival epithelial cell lines show, using an unbiased gene microarray approach, unique gene expression signatures that differ from primary conjunctival epithelial cells (PCEC) and conjunctival tissue. Globally, the expression profile obtained with the Affymetrix U133A chip (>22000 genes) from PCEC was clustered more closely to conjunctival tissue than either of the 2 cell lines. However, when restricted to Gene Ontology sub-categories: cellular defense, viral replication/cycling, antigen presentation, anti-oxidant pathways and ubiquitin ligase complex, the cell lines correlated reasonably well to PCEC (r > 0.70). In the category response to inflammation, correlation of cell lines to PCEC was poor (r = -0.012 and 0.041 for IOBA-NHC and ChWK respectively). In general, the expression profile in IOBA-NHC cells was better correlated to PCEC than the ChWK cells. This was statistically significant (p<0.05) when one considers all the genes on the chip, or for proteins in the extracellular region, response to wounding, stress, lipid, protein and organic acid metabolism, development and differentiation. Our results are useful for the choice of conjunctival cell lines, if necessary, in future experiments, to increase validity of extrapolation to clinical scenarios.
Comparison of gene expression profiles of conjunctival cell lines with primary cultured conjunctival epithelial cells and human conjunctival tissue.
No sample metadata fields
View SamplesLgr5+ adult intestinal stem cells are highly proliferative throughout life. Single Lgr5+ stem cells can be cultured into 3D epithelial organoids containing all cell types at nearnormal ratios. Culture conditions to generate the main cell types have been established previously, but signals inducing the various types of enteroendocrine cells (EECs) have remained elusive. Here we generate quiescent Lgr5+ stem cells in vitro by inhibition of the EGF-receptor (EGFR) and mitogen-associated protein kinase (MAPK) signaling pathways in organoids, a state that can be readily reversed. Quiescent Lgr5+ stem cells gain a distinct molecular signature, biased towards EEC differentiation. Indeed, combined inhibition of Wnt, Notch and MAPK pathways efficiently generates a diversity of EEC subtypes in vitro. Our observations uncouple Wnt-dependent stem cell maintenance from EGF-dependent proliferation and cell fate choice, and provide an in vitro approach for the study of the elusive EECs. Overall design: We established a stable culture of quiescent Lgr5+ intestinal stem cells in culture. These highly resemble quiescent secretory precursors, which has high EEC differentiation potential. Following on this lead, we elucidated what signals are required to generate EEC cells of all varieties, and provide a method to produce these EEC cells in large numbers.
Induced Quiescence of Lgr5+ Stem Cells in Intestinal Organoids Enables Differentiation of Hormone-Producing Enteroendocrine Cells.
Specimen part, Cell line, Subject
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