During development, lineage specification is controlled by several signaling pathways involving various transcription factors (TFs). Here, we studied the RE1-silencing transcription factor (REST) and identified an important role of this TF in cardiac differentiation. Using mouse embryonic stem cells (ESC) to model development, we analyzed the effect of REST knock-out on the ability to these cells to differentiate into the cardiac lineage. Detailed analysis of specific lineage markers expression showed selective down-regulation of endoderm markers in REST-null cells, thus contributing to a loss of cardiogenic signals.
A Role for RE-1-Silencing Transcription Factor in Embryonic Stem Cells Cardiac Lineage Specification.
Specimen part, Treatment
View SamplesTo explore putative connections between genetic methionine restriction and the retrograde response, we asked whether the altered transcriptional program of methionine-restricted cells required RTG3 (which is indispensible for retrograde signaling in yeast).
Methionine restriction activates the retrograde response and confers both stress tolerance and lifespan extension to yeast, mouse and human cells.
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View SamplesThe human Werner and Bloom syndromes (WS and BS) are caused by deficiencies in the WRN and BLM RecQ helicases, respectively. WRN, BLM and their S. cerevisiae homologue Sgs1, are particularly active in vitro in unwinding G-quadruplex DNA (G4-DNA), a family of non-canonical nucleic acid structures formed by certain G-rich sequences. Recently, mRNA levels from loci containing potential G-quadruplex-forming sequences (PQS) were found to be preferentially altered in sgs1 mutants, suggesting that G4-DNA targeting by Sgs1 directly affects gene expression. Here, we extend these findings to human cells. Using microarrays to measure mRNAs obtained from human fibroblasts deficient for various RecQ family helicases, we observe significant associations between loci that are upregulated in WS or BS cells and loci that have PQS. No such PQS associations were observed for control expression datasets, however. Furthermore, upregulated genes in WS and BS showed no or dramatically reduced associations with sequences similar to PQS but that have considerably reduced potential to form intramolecular G4-DNA. These findings indicate that, like Sgs1, WRN and BLM can regulate transcription globally by targeting G4-DNA.
Altered gene expression in the Werner and Bloom syndromes is associated with sequences having G-quadruplex forming potential.
Sex, Age, Race
View SamplesIn Xenopus laevis, a number of studies identified vegetal factors that specify the germ line, endoderm and dorsal axis, but there are few studies demonstrating roles for animal-enriched maternal mRNAs.
Novel animal pole-enriched maternal mRNAs are preferentially expressed in neural ectoderm.
Specimen part
View SamplesGlioblastoma HSR-GBM1 cells have low mitochondrial DNA copy numbers which is associated with the abnormal DNA methylation patterns. By inducing DNA demthylation using 5azacytidine and vitamin C, HSR-GBM1 cells modulate their mitochondrial copy number and capability of differentiation. Overall design: HSR-GBM1 cell line with three conditions: untreated control group, treated with 5 azacitidine and treated with vitamin C. 3 biological replicates of each condition.
Global DNA methylation synergistically regulates the nuclear and mitochondrial genomes in glioblastoma cells.
Specimen part, Cell line, Subject
View SamplesAnti-retroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection from a fatal illness to a chronic condition by controlling viral replication and restoring immune function. However, chronic T-cell activation can be observed in 20-35% of individuals on ART, resulting in an immune reconstitution inflammatory syndrome (IRIS) [1-3]. IRIS involving the CNS can result in permanent disability and death [4]. Tat is a viral protein produced in HIV-infected cells and released into the extracellular space [5]. We show that the secreted-Tat protein activated uninfected T-cells in an antigen-independent manner without inducing proliferation. Notably, Tat induced the secretion of IL-17 from T-cells and increased the percentage of T-cells with a Th17 phenotype. T-cell activation was independent of the T-cell receptor but dependent on endocytosis of Tat and activation of vascular endothelial growth factor receptor 2 (VEGFR2). Tat induced global changes in histone acetylation and increased HIV infection in non-replicating T-cells. Furthermore, in an individual with CNS IRIS, Tat expressing infiltrates and secretion of IL-17 was detected in the absence of viral replication in the brain. Thus Tat can induce T-cell activation in a paracrine and autocrine manner resulting in propagation of inflammation and increased virulence.
Induction of IL-17 and nonclassical T-cell activation by HIV-Tat protein.
Specimen part, Treatment, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Global gene expression analysis of amniotic fluid cell-free RNA from recipient twins with twin-twin transfusion syndrome.
Sex
View SamplesTo understand the biological pathways involved in twin-twin transfusion syndrome (TTTS) by performing global gene expression analysis of amniotic fluid (AF) cell-free RNA
Global gene expression analysis of amniotic fluid cell-free RNA from recipient twins with twin-twin transfusion syndrome.
Sex
View SamplesTo understand the biological pathways involved in twin-twin transfusion syndrome (TTTS) by performing global gene expression analysis of amniotic fluid (AF) cell-free RNA
Global gene expression analysis of amniotic fluid cell-free RNA from recipient twins with twin-twin transfusion syndrome.
Sex
View SamplesLoss of Syk in normal breast cells in vivo and in vitro: gene expression and phenotypic switch to stem-cell like with induction of invadopodia
Tumor suppressor function of Syk in human MCF10A in vitro and normal mouse mammary epithelium in vivo.
Cell line
View Samples