To gain insights into the molecular pathogenesis of DCM caused by LMNA mutation, a doxycycline-inducible (Dox-Off) gene expression system was used to express either a wild type (WT) or a mutant LMNA containing the pathogenic variant p.Asp300Asn (LMNAD300N) in cardiac myocytes. The LMNAD300N is associated with DCM in patients with atypical progeroid/Werner syndrome and non-syndromic cardiac progeria. Expression of the mutant LMNAD300N protein in cardiac myocytes led to severe fibrosis, apoptosis, cardiac dysfunction, and premature death. RNA-seq was performed (prior to onset of cardiac dysfunction) to identify gene signatures and transcriptional regulators responsible for this phenotype. Mechanistic studies identified activation of E2F/TP53/DDR, as a major mechanism responsible for the pathogenesis of DCM caused by the LMNAD300N mutation. Overall design: RNA-seq analysis from 2-week old WT and mice expressing mutant LMNA (LMNAD300N)
DNA Damage Response/TP53 Pathway Is Activated and Contributes to the Pathogenesis of Dilated Cardiomyopathy Associated With LMNA (Lamin A/C) Mutations.
Cell line, Subject
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.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
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
View SamplesOur previous studies have shown that C/EBP plays a critical role in human endometrial stromal decidualization. In order to identify the molecular pathways regulated by C/EBP during decidualization, we performed gene expression profiling using RNA isolated from normal and C/EBP-deficient human endometrial stromal cells. The microarray results revealed that several key regulators of stromal differentiation, such as BMP2, Wnt4, IL-11R and STAT3, operate downstream of C/EBP during decidualization. Further studies revealed that STAT3 is a direct target of C/EBP and plays an important role in cytokine signal during the decidualization process. Gene expression profiling, using STAT3-deficient HESCs, showed an extensive overlap of pathways downstream of STAT3 and C/EBP during stromal cell differentiation.
Regulation of human endometrial stromal proliferation and differentiation by C/EBPβ involves cyclin E-cdk2 and STAT3.
Specimen part
View SamplesEpithelial cells provide an initial line of defense against damage and pathogens in barrier tissues such as the skin; however this balance is disrupted in obesity and metabolic disease. Skin gamma delta T cells recognize epithelial damage and release cytokines and growth factors that facilitate wound repair. To determine the impact of obesity and metabolic disease on skin gamma delta T cells, we isolated skin gamma delta T cells from 10-week old C57BLKS/J lean db/+ and obese db/db animals for further study. Due to a deficiency in the leptin receptor (db), homozygous db/db animals do not process satiety signals, continually eat and develop severe obesity and metabolic disease. Skin gamma delta T cells isolated from these animals were compared for changes in mRNA expression using microarray. We have determined that obesity and metabolic disease negatively impacts homeostasis and functionality of skin gamma delta T cells, rendering host defense mechanisms vulnerable to injury and infection.
Gammadelta T cells are reduced and rendered unresponsive by hyperglycemia and chronic TNFalpha in mouse models of obesity and metabolic disease.
No sample metadata fields
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