Hematopoietic differentiation is strictly regulated by complex network of transcription factors that are controlled by ligands binding to cell surface receptors. Disruptions of the intricate sequences of transcriptional activation and suppression of multiple genes cause hematological diseases, such as leukemias, myelodysplastic syndromes or myeloproliferative syndromes. From a clinical standpoint, deciphering the pattern of gene expression during hematopoiesis may help unravel disease-specific mechanisms in hematopoietic malignancies. Herein, we describe a human in vitro hematopoietic model system where lineage specific differentiation of CD34+ cells was accomplished using specific cytokines. Microarray and RNAseq based whole transcriptome and exome analysis was performed on the differentiated erythropoietic, granulopoietic and megakaryopoietic cells to delineate changes in expression of whole transcripts and exons. Analysis on the Human 1.0 ST exon arrays indicated differential expression of 172 genes (P< 0.0000001) and significant splicing of 86 genes during differentiation. Pathway analysis identified these genes to be involved in Rac/RhoA signaling, Wnt/B-catenin signaling and alanine/aspartate metabolism. Comparison of the microarray data to next generation RNAseq analysis during erythroid differentiation demonstrated a high degree of correlation in gene (R= 0.72) and exon (R=0. 62) expression. Our data provides a molecular portrait of events that regulate differentiation of hematopoietic cells. Knowledge of molecular processes by which the cells acquire their cell specific fate would be beneficial in developing cell-based therapies for human diseases.
Transcriptome profiling and sequencing of differentiated human hematopoietic stem cells reveal lineage-specific expression and alternative splicing of genes.
Specimen part
View SamplesExpression profiling using a defined set of iron regulated genes identifies co-regulation of genes and pathways related to inflammatory cytokines
Iron, inflammation, and early death in adults with sickle cell disease.
Specimen part, Disease
View SamplesWe have tested the effect of iron on the gene expression profile in human leukemia cells with properties of erythroid differentiation.
Heme-bound iron activates placenta growth factor in erythroid cells via erythroid Krüppel-like factor.
Specimen part
View SamplesThe experiment was designed to generate a time series for epithelial model during development. Each time point had 3 replicates. The data set contained 5 time points over 10 days. They are day0, day3, day5,day7,day10.
Dynamic and physical clustering of gene expression during epidermal barrier formation in differentiating keratinocytes.
Age, Specimen part, Time
View SamplesThe conserved Mef2 transcription factor is a major regulator of gene expression and differentiation. Recent genomic studies have identified a large number of mef2-regulated target genes with distinct temporal expression profiles during Drosophila myogenesis. However, the question remains as to how a single transcription factor can control such diverse patterns of gene expression. The aim of this project was to investigate whether there are genes with different mef2-requirements for their expression during muscle differentiation in vivo during the development of Drosophila melanogaster.
mef2 activity levels differentially affect gene expression during Drosophila muscle development.
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Genome-wide mapping of DNA hydroxymethylation in osteoarthritic chondrocytes.
Specimen part
View SamplesExamination of the genome-wide distribution of 5hmC in osteoarthritic chondrocytes compared to normal chondrocytes in order to elucidate the effect on OA-specific gene expression.
Genome-wide mapping of DNA hydroxymethylation in osteoarthritic chondrocytes.
Specimen part
View SamplesThe Human T-cell Leukemia Virus (HTLV)-type-I non-structural protein p30 plays an important role in virus transmission and gene regulation. p30 has been documented to inhibit the export of certain viral mRNA transcripts from the nucleus to the cytoplasm. This nuclear retainment of RNA molecules essentially results in gene silencing, where protein products are not produced.
Genome wide analysis of human genes transcriptionally and post-transcriptionally regulated by the HTLV-I protein p30.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure.
Age, Specimen part
View SamplesBisphenol-A (BPA) is an environmentally ubiquitous estrogen-like endocrine-disrupting compound. Exposure toBPAin utero hasbeen linked to female reproductive disorders, including endometrial hyperplasia and breast cancer. Estrogens are an etiological factor in many of these conditions. We sought to determine whether in utero exposure to BPA altered the global CpG methylation pattern of the uterine genome, subsequent gene expression, and estrogen response. Pregnant mice were exposed to an environmentally relevant dose of BPA or DMSO control. Uterine DNA and RNA were examined by using methylated DNA immunoprecipitation methylation microarray, expression microarray, and quantitative PCR. In utero BPA exposure altered the global CpG methylation profile of the uterine genome and subsequent gene expression. The effect on gene expression was not apparent until sexual maturation, which suggested that estrogen response was the primary alteration. Indeed, prenatal BPA exposure preferentially altered adult estrogen-responsive gene expression. Changes in estrogen response were accompanied by altered methylation that preferentially affected estrogen receptor-a (ERa)binding genes. The majority of genes that demonstrated both altered expression and ERa binding had decreased methylation. BPA selectively altered the normal developmental programming of estrogen-responsive genes via modification of the genes that bind ERa. Gene environment interactions driven by early life xenoestrogen exposure likely contributes to increased risk of estrogen related disease in adults.Jorgensen, E. M.,Alderman,M.H., III,Taylor, H. S. Preferential epigenetic programmingof estrogen response after in utero xenoestrogen (bisphenol-A) exposure.
Preferential epigenetic programming of estrogen response after in utero xenoestrogen (bisphenol-A) exposure.
Age, Specimen part
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