Myocardial infarction (MI) often results in left ventricular (LV) remodeling followed by heart failure (HF). It is of great clinical importance to understand the molecular mechanisms that trigger transition from compensated LV injury to HF and to identify relevant diagnostic biomarkers. In this study, we performed transcriptional profiling of LVs in rats with a wide range of experimentally induced infarct sizes and of peripheral blood mononuclear cells (PBMCs) in animals that developed HF.
Transcriptional profiling of left ventricle and peripheral blood mononuclear cells in a rat model of postinfarction heart failure.
Specimen part
View SamplesWe have observed that follicular B cells from mice with a hypomorphic mutation (IkL/L) in the Ikzf1 gene (which encodes the Ikaros transcription factor) exhibit an increased proliferative response to anti-IgM stimulation (Kirstetter et al, Eur J Immunol, 32:720-30, 2002). We asked if Ikaros controls the transcriptional response that unfolds after activation, or if differences in the transcriptional landscape of resting B cells could explain the altered response. To this end, we have determined the transcriptome of unstimulated WT and IkL/L follicular B cells, as well as that of cells stimulated for 3h and 12h with anti-IgM. Samples from 2 independent experients were analyzed.
Ikaros limits follicular B cell activation by regulating B cell receptor signaling pathways.
Age, Specimen part
View SamplesExpression data from antigen-experienced Nfat1+/+ and Nfat1-/- CD4+ T cells following 21 days of Plasmodium yoelii 17XNL infection.
The Transcription Factor NFAT1 Participates in the Induction of CD4<sup>+</sup> T Cell Functional Exhaustion during Plasmodium yoelii Infection.
Sex, Specimen part
View SamplesThe Drosha-DGCR8 complex (Microprocessor) is required for microRNA (miRNA) biogenesis. DGCR8 contains two double-stranded RNA binding motifs that recognize the RNA substrate, whereas Drosha functions as the endonuclease. We have used high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) to identify endogenous RNA targets of DGCR8 in mammalian cells. Unexpectedly, miRNAs were not the most abundant targets. DGCR8-bound RNAs comprised several hundred mRNAs as well as snoRNAs and long non-coding RNAs. We found that DGCR8 together with Drosha controls the abundance of several mRNAs, as well as long non-coding RNAs, such as MALAT-1. By contrast, the DGCR8-mediated cleavage of snoRNAs is independent of Drosha, suggesting the involvement of DGCR8 in cellular complexes with other endonucleases. Interestingly, binding of DGCR8 to cassette exons, acts as a novel mechanism to regulate the relative abundance of alternatively spliced isoforms. Collectively, these data provide new insights in the complex role of DGCR8 in controlling the fate of several classes of RNAs. Overall design: Comparison of RNAs associated to both endogenous (D8) and overexpressed (T7) DGCR8 in HEK293T cells
Drosha regulates gene expression independently of RNA cleavage function.
Cell line, Subject
View SamplesWe compare the CD4+ T cell transcriptome between obese and normal-weight children with asthma to identify molecules/pathways differentially expressed in obese asthmatic CD4+ T cells Overall design: CD4+ T cell transcriptome generated using Directional RNA-Seq library preparatio; A=Normal-weight, B=obese
CDC42-related genes are upregulated in helper T cells from obese asthmatic children.
Sex, Age, Specimen part, Disease stage, Race, Subject
View SamplesThe experiment aimed at determining the genes that are under the control of the Ikaros transcription factor in mouse splenic B1 and B2 B lymphocyte subsets. To this aim, we used Ikf/f R26-CreERT2+ (Cre+) or Ikf/f R26-CreERT2- (Cre-) mice, which correspond to mice with floxed null alleles for Ikzf1 (Heizmann et al., JEM 210:2823-32, 2013) that were crossed with the R26-CreERT2 mice, which harbor a knock-in of the cDNA encoding the tamoxifen (TAM) inducible CreERT2 recombinase in the Rosa26 gene (Badea et al, J. Neurosci 23:2314-22, 2003). 6-8 week-old mice were injected daily with TAM for 3d (50mg/kg). Mice were sacrificed 10d after the first injection, and splenic B1 and B2 B cell populations sorted by flow cytometry.
Ikaros Is a Negative Regulator of B1 Cell Development and Function.
Sex, Specimen part
View SamplesWe identify sites of combinatorial control by performing high throughput ChIP experiments on p300, CREB-binding protein (CBP), the deacetylase SIRT1 and on multiple DNA-binding transcription factors in three different tissues. We present a quantitative model of transcriptional regulation that reveals the contribution of each binding site to tissue-specific gene expression in several mouse cell types. Binding to both evolutionarily conserved and non-conserved sequences is found to contribute significantly to transcriptional regulation. We demonstrate that binding location strongly predicts the expression level of nearby genes.
A quantitative model of transcriptional regulation reveals the influence of binding location on expression.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Novel subtype-specific genes identify distinct subpopulations of callosal projection neurons.
Specimen part
View Samples3 subtypes of cortical projection neurons were purified by fluorescence-activated cell sorting (FACS) at 4 different stages of development from mouse cortex. A detailed description of the data set is described in Arlotta, P et al (2005) and Molyneaux, BJ et al (2009). The hybridization cocktails used here were originally applied to the Affymetrix mouse 430A arrays and submitted as GEO accession number GSE2039. The same hybridization cocktails were then applied to the Affymetrix mouse 430 2.0 arrays, and those data are contained in this series.
Novel subtype-specific genes identify distinct subpopulations of callosal projection neurons.
Specimen part
View SamplesMechanical forces are essential for normal fetal lung development. However, the cellular and molecular mechanisms regulating this process remain largely unknown. In the present study, we used oligonucleotide microarray technology to investigate gene expression profile in cultured E19 rat fetal lung type II epithelial cells exposed to a level of mechanical strain similar to that observed in utero. Significance Analysis of Microarrays (SAM) identified 92 genes differentially expressed by strain. Interestingly, several members of the solute carrier family of amino acid transporters, genes involved in amino acid synthesis and development, and amiloride-sensitive epithelial sodium channel gene were induced by strain. These results were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Thus, this study identifies genes induced by strain that may be important for amino acid signaling pathways, protein synthesis and development in fetal type II cells. In addition, these data suggest that mechanical forces may contribute to facilitate lung fluid reabsorption in preparation for birth. Taken together, the present investigation provides further insights into how mechanical forces may modulate fetal lung development.
DNA microarray reveals novel genes induced by mechanical forces in fetal lung type II epithelial cells.
Sex, Specimen part
View Samples