A causal role of mutations in genes encoding for multiple general transcription factors in neurodevelopmental disorders including autism suggested that alterations at the global level of gene expression regulation might also relate to disease risk in sporadic cases of autism. This premise can be tested by evaluating for global changes in the overall distribution of gene expression levels. For instance, in mice, we recently showed that variability in hippocampal-dependent behaviors was associated with variability in the pattern of the overall distribution of gene expression levels, as assessed by variance in the distribution of gene expression levels in the hippocampus. We hypothesized that a similar change in the variance in gene expression levels might be found in children with autism. Gene expression microarrays covering greater than 47,000 unique RNA transcripts were done on purified RNA from peripheral blood lymphocytes of children with autism (n=82) and controls (n=64). The variance in the distribution of gene expression levels from each microarray was compared between groups of children. Also tested was whether a risk factor for autism, increased paternal age, was associated with variance in the overall distribution of gene expression levels. A decrease in the variance in the distribution of gene expression levels in peripheral blood lymphocytes (PBL) was associated with the diagnosis of autism and a risk factor for autism, increased paternal age. Traditional approaches to microarray analysis of gene expression suggested a possible mechanism for decreased variance in gene expression. Gene expression pathways involved in transcriptional regulation were down-regulated in the blood of children with autism and children of older fathers. Thus, results from global and gene specific approaches to studying microarray data were complimentary and supported the hypothesis that alterations at the global level of gene expression regulation are related to autism and increased paternal age. Regulation of transcription, thus, represents a possible point of convergence for multiple etiologies of autism and other neurodevelopmental disorders.
Autism and increased paternal age related changes in global levels of gene expression regulation.
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View SamplesThe goal of this study was to investigate the role of intragenic CTCF in alternative pre-mRNA splicing through a combined CTCF-ChIP-seq and RNA-seq approach. CTCF depletion led to decreased inclusion of weak upstream exons. Overall design: CTCF ChIP-seq was performed in BJAB and BL41 B cell lines and normalized relative to Rabbit Ig control IP-seq reads. RNA-seq was performed in BJAB and BL41 cells transduced with shRNA against CTCF or RFP as a control, and in untransduced cells as well.
CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing.
Cell line, Subject
View SamplesWe have determined that verticillin A is a histone methyltransfease inhibitor that selectively inhibits human SUV39H1, SUV39H2, G9a and GLP to inhibit H3K9 methylation in human colon cancer cells. The objective here is to identify verticillin A target genes in human colon cancer cells.
H3K9 Trimethylation Silences Fas Expression To Confer Colon Carcinoma Immune Escape and 5-Fluorouracil Chemoresistance.
Cell line, Treatment
View SamplesSilymarin (SM) is a popular botanical medicine with purported liver protective effects. SM displays multiple effects in animal models and in cell culture including prevention of liver disease, reduction of inflammation, oxidative stress, and proliferation. Despite a plethora of data indicating that SM impinges on multiple cellular signaling pathways important in inflammation and disease, no unifying mechanisms have been forwarded. To define how SM elicits so many biological effects, the current study presents the first comprehensive transcriptional profiling study of human hepatoma cells treated with SM. The intention of the study was to focus on the early transcriptional events that are associated with SM-induced inhibition of proliferation and inflammation. Collectively, the data demonstrate that SM causes a rapid transcriptional reprogramming of cells that initially manifests as energy stress and slowing of cellular metabolism, leading to inhibition of cell growth and inflammation.
Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling.
Specimen part, Cell line, Treatment, Time
View SamplesWe studied changes in a whole transcriptome during dsDNA virus infection. Overall design: Fibroblasts (MRC5 & HFF) and epithelial cells (ARPE19) were infected with HCMV, HSV1 or Ad5 and total RNA was isolated at 48, 9, or 24 hpi, respectively. Total 15 treatments were used. There were 2 biological replicates analyzed per each treatment.
A tumor-specific endogenous repetitive element is induced by herpesviruses.
Specimen part, Subject
View SamplesWe studied changes in a whole transcriptome during HCMV infection. Overall design: Fibroblasts (MRC5) were infected with HCMV and total RNA was isolated at 48. Total 2 individual samples were used. There were 3 replicates analyzed per individual sample.
A tumor-specific endogenous repetitive element is induced by herpesviruses.
Specimen part, Subject
View SamplesDuring cortical development, distinct subtypes of glutamatergic neurons are sequentially born and differentiate from dynamic populations of progenitors. How progenitors and their daughter cells are temporally patterned remains unknown. Here, we trace the transcriptional trajectories of successive generations of apical progenitors (APs) and isochronic cohorts of their daughter neurons in the developing mouse neocortex using high temporal resolution parallel single-cell RNA sequencing. We identify and functionally characterize a core set of evolutionarily-conserved temporally patterned genes which drive APs from internally-driven states to more exteroceptive states, revealing a progressively increasing role for extracellular signals as corticogenesis unfolds. These embryonic age-dependent AP molecular states are reflected in their neuronal progeny as successive ground states, onto which essentially conserved early post-mitotic differentiation programs are applied. Thus, temporally unfolding molecular birthmarks present in progenitors act in their post-mitotic progeny as seeds for adult neuronal diversity. Overall design: Investigation of the transcriptional dynamics in time-locked cohorts of cortical cells across embryonic neurogenesis. Flashtag is injected at 4 ages (E12, E13, E14, E15), and cells collected 1H, 24H, 96H after birth (= a total of 12 conditions) and analyzed by single cell transcriptomics.
Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The effects of EBV transformation on gene expression levels and methylation profiles.
Sex, Specimen part, Subject
View SamplesEpstein-Barr virus (EBV) transformed lymphoblastoid cell lines (LCLs) are a widely used renewable resource for functional genomic studies in humans. The ability to accumulate multidimensional data pertaining to the same individual cell lines, from complete genomic sequences to detailed gene regulatory profiles, further enhances the utility of LCLs as a model system. However, the extent to which LCLs are a faithful model system is relatively unknown. We have previously shown that gene expression profiles of newly established LCLs maintain a strong individual component. Here, we extend our study to investigate the effect of freeze-thaw cycles on gene expression patterns in mature LCLs, especially in the context of inter-individual variation in gene regulation. We found a profound difference in the gene expression profiles of newly established and mature LCLs. Once newly established LCLs undergo a freeze-thaw cycle, the individual specific gene expression signatures become much less pronounced as the gene regulatory programs in LCLs from different individuals converge to a more uniform profile, which reflects a mature transformed B cell phenotype. As expected, previously identified eQTLs are enriched among the relatively few genes whose regulations in mature LCLs maintain marked individual signatures. We thus conclude that findings and insight drawn from gene regulatory studies in mature LCLs are generally not affected by artificial nature of the LCL model system and are likely to faithfully reflect regulatory interactions in primary tissues. However, our data indicate that many aspects of primary B cell biology cannot be observed and studied in mature LCL cultures.
The effect of freeze-thaw cycles on gene expression levels in lymphoblastoid cell lines.
Sex, Specimen part
View SamplesEpstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) provide a conveniently accessible and renewable resource for functional studies in humans. The ability to accumulate multidimensional data pertaining to the same individual cell lines, from complete genomic sequences to detailed gene regulatory profiles, further enhances the utility of LCLs as a model system. A lingering concern, however, is that the changes associated with EBV transformation of LCLs reduce the usefulness of LCLs as a surrogate model for primary tissues. To evaluate the validity of this concern, we compared global gene expression profiles between CD20+ primary B cells and CD3+ primary T cells sampled from six individuals. Six independent replicates of transformed LCLs were derived from each sample.
The effects of EBV transformation on gene expression levels and methylation profiles.
Sex, Specimen part, Subject
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