Identification of genes differentially expressed between the neonatal heart of a genetic rat model of cardiac hypertrophy (the Hypertrophic Heart Rat, HHR) and the control (the Normal Heart Rat, NHR) using Affymetrix GeneChip Rat Gene 1.0 ST Arrays.
No associated publication
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of key regions and genes important in the pathogenesis of sezary syndrome by combining genomic and expression microarrays.
Specimen part, Disease
View SamplesThis study used tumour and paired normal samples from 28 Szary Syndrome (SS) patients to define recurrent regions of chromosomal aberrations. Our data identified recurrent losses of 17p13.2-p11.2 and 10p12.1-q26.3 occurring in 71 and 68% of cases respectively; common gains were detected for 17p11.2-q25.3 (64%) and chromosome 8/8q (50%). Moreover, we identified novel genomic lesions recurring in more than 30% of tumours: loss of 9q13-q21.33 and gain of 10p15.3-10p12.2. In the Szary Syndrome cases analysed, we could find several small and few large Uniparental Disomies involving interstitial or telomeric regions of LOH occurring mainly for chromosome 10 and to a lesser extent for chromosome 9 and 17. In the attempt to correlate Copy Number data and clinical parameters we find a relationship between complex pattern of chromosomal aberrations, involving at least three recurrent Copy Number alterations, and shorter survival. Integrating mapping and transcriptional data we were able to identify a total of 113 deregulated transcripts in aberrant chromosomal regions that included cancer related genes such as members of the NF-kB pathway (BAG4, BTRC, NKIRAS2, PSMD3, TRAF2) that might explain its constitutive activation in CTCL. Matching this list of genes with those discriminating patients with different survival times we identify several common candidates that might exert critical roles in Szary Syndrome, like BUB3 and PIP5K1B.
Identification of key regions and genes important in the pathogenesis of sezary syndrome by combining genomic and expression microarrays.
Specimen part, Disease
View SamplesTcl1 is known to be involved in survival, proliferation and differentiation of human lymphocytes and mouse embryonic stem cells. Loss of Tcl1 gene in the KO mouse model affects skin integrity inducing alopecia and ulcerations.
T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1.
Specimen part
View SamplesPulmonary fibrosis develops as a consequence of environmentally induced lung injury and/or an inherent disease susceptibility causing fibroblast activation, proliferation and extracellular matrix deposition.
Microarray profiling reveals suppressed interferon stimulated gene program in fibroblasts from scleroderma-associated interstitial lung disease.
Specimen part, Disease
View SamplesUnderstanding the transcriptional regulation of pluripotent cells is of fundamental interest and will greatly inform efforts aimed at directing differentiation of embryonic stem (ES) cells or reprogramming somatic cells. We first analyzed the transcriptional profiles of mouse ES cells and primordial germ cell (PGCs) and identified genes up-regulated in pluripotent cells both in vitro and in vivo. These genes are enriched for roles in transcription, chromatin remodeling, cell cycle and DNA repair. We developed a novel computational algorithm, CompMoby, which combines analyses of sequences both aligned and non-aligned between different genomes with a probabilistic segmentation model to systematically predict short DNA motifs that regulate gene expression. CompMoby was used to identify conserved over-represented motifs in genes up-regulated in pluripotent cells. We show that the motifs are preferentially active in undifferentiated mouse ES and Embryonic Germ cells in a sequence-specific manner, and that they can act as enhancers in the context of an endogenous promoter. Importantly, the activity of the motifs is conserved in human ES cells. We further show that the transcription factor NF-Y specifically binds to one of the motifs, is differentially expressed during ES cell differentiation and is required for ES cell proliferation. This study provides novel insights into the transcriptional regulatory networks of pluripotent cells. Our results suggest that this systematic approach can be broadly applied to understanding transcriptional networks in mammalian species.
Systematic identification of cis-regulatory sequences active in mouse and human embryonic stem cells.
Age, Specimen part, Time
View SamplesThis is polyA mRNA-seq of a clonal MIN6 beta cell line that expresses EGFP under the control of the insulin promoter and mCherry under control of the RSV promoter.
No associated publication
Sex, Specimen part
View SamplesCardiogenesis involves multiple biological processes acting in concert during development, a coordination achieved by the regulation of diverse cardiac genes by a finite set of transcription factors (TFs). Previous work from our laboratory identified the roles of two Forkhead TFs, Checkpoint suppressor homologue (CHES-1-like) and Jumeau (Jumu) in governing cardiac progenitor cell divisions by regulating Polo kinase activity. These TFs were also implicated in the regulation of numerous other cardiac genes. Here we show that these two Forkhead TFs play an additional and mutually redundant role in specifying the cardiac mesoderm (CM): eliminating the functions of both CHES-1-like and jumu in the same embryo results in defective hearts with missing hemisegments. Our observations indicate that this process is mediated by the Forkhead TFs regulating the fibroblast growth factor receptor Heartless (Htl) and the Wnt receptor Frizzled (Fz), both previously known to function in cardiac progenitor specification: CHES-1-like and jumu exhibit synergistic genetic interactions with htl and fz in CM specification, thereby implying function through the same genetic pathways, and transcriptionally activate the expression of both receptor-encoding genes. Furthermore, ectopic overexpression of either htl or fz in the mesoderm partially rescues the defective CM specification phenotype seen in embryos doubly homozygous for mutations in jumu and CHES-1-like. Together, these data emphasize the functional redundancy that leads to robustness in the cardiac progenitor specification process mediated by Forkhead TFs regulating the expression of signaling pathway receptors, and illustrate the pleiotropic functions of this class of TFs in different aspects of cardiogenesis.
Two forkhead transcription factors regulate the division of cardiac progenitor cells by a Polo-dependent pathway.
Specimen part
View SamplesThe development of a complex organ requires the specification of appropriate numbers of each of its constituent cell types, as well as their proper differentiation and correct positioning relative to each other. During Drosophila cardiogenesis, all three of these processes are controlled by jumeau (jumu) and Checkpoint suppressor homologue (CHES-1-like), two genes encoding forkhead transcription factors that we discovered utilizing an integrated genetic, genomic and computational strategy for identifying novel genes expressed in the developing Drosophila heart. Both jumu and CHES-1-like are required during asymmetric cell division for the derivation of two distinct cardiac cell types from their mutual precursor, and in symmetric cell divisions that produce yet a third type of heart cell. jumu and CHES-1-like control the division of cardiac progenitors by regulating the activity of Polo, a kinase involved in multiple steps of mitosis. This pathway demonstrates how transcription factors integrate diverse developmental processes during organogenesis.
Two forkhead transcription factors regulate the division of cardiac progenitor cells by a Polo-dependent pathway.
Specimen part
View SamplesThe development of a complex organ requires the specification of appropriate numbers of each of its constituent cell types, as well as their proper differentiation and correct positioning relative to each other. During Drosophila cardiogenesis, all three of these processes are controlled by jumeau (jumu) and Checkpoint suppressor homologue (CHES-1-like), two genes encoding forkhead transcription factors that we discovered utilizing an integrated genetic, genomic and computational strategy for identifying novel genes expressed in the developing Drosophila heart. Both jumu and CHES-1-like are required during asymmetric cell division for the derivation of two distinct cardiac cell types from their mutual precursor, and in symmetric cell divisions that produce yet a third type of heart cell. jumu and CHES-1-like control the division of cardiac progenitors by regulating the activity of Polo, a kinase involved in multiple steps of mitosis. This pathway demonstrates how transcription factors integrate diverse developmental processes during organogenesis.
Two forkhead transcription factors regulate the division of cardiac progenitor cells by a Polo-dependent pathway.
Specimen part
View Samples