Here we analyse single cell transcriptome profiles of EZH2-deficient human embroynic stem cells Overall design: Single cell transcriptome (mRNA-Seq) from Ezh2-/- (Null) and EZH2+/+ (WT) human ESC
Deletion of the Polycomb-Group Protein EZH2 Leads to Compromised Self-Renewal and Differentiation Defects in Human Embryonic Stem Cells.
Specimen part, Subject
View SamplesThe goal of this study was to identify the transcriptional mechanisms involved in the activation of the immune system by QS-21, a triterpene glycoside purified from the bark of Quillaja saponaria which has adjuvant activity in vivo. Saponins represent a promising class of vaccine adjuvant. Together with the TLR4-ligand MPL, QS-21 is part of the Adjuvant System AS01, a key component of the Malaria and Zoster candidate vaccines that display demonstrated clinical efficacy. However, the mechanism of action of QS-21 in this liposomal formulation is poorly understood. Upon intra-muscular immunisation, we observed that QS-21 rapidly accumulated in CD169+ resident macrophages of the draining lymph node where it elicited a local innate immune response. Depletion of these cells abrogated QS-21-mediated innate cell recruitment to the lymph node, dendritic cell (DC) phenotypic maturation as well as the adjuvant effect on T cell and antibody responses to co-administered antigens. DCs rather than lymph node-resident macrophages were directly involved in T cell priming by QS-21 as revealed by the decrease in antigen-specific T cell response in Batf3/ mice. Further analysis showed that the adjuvant effect of QS-21 depended on the integration of Caspase-1 and MyD88 pathways, at least in part through the local release of HMGB1. Taken together, this work unravels the key role of lymph node sentinel macrophage in controlling the adjuvant effect of a molecule proven to improve vaccine response in humans
Central Role of CD169<sup>+</sup> Lymph Node Resident Macrophages in the Adjuvanticity of the QS-21 Component of AS01.
Specimen part
View SamplesIn response to UVB irradiation, human keratinocytes transiently block cell cycle progression to allow ample time for DNA repair and cell fate determination. These cellular processes are important for evading the initiation of carcinogenesis in skin. We previously showed that repression of mRNA translation initiation through phosphorylation of eIF2a (eIF2a-P) protects keratinocytes from UVB-induced apoptosis. In this study, we elucidate the mechanism of eIF2a-P cytoprotection in response to UVB. Loss of eIF2a-P induced by UVB diminished G1 arrest, DNA repair rate, and cellular senescence coincident with enhanced cell death in human keratinocytes. Genome-wide translation analyses revealed that the mechanism for these critical changes directed by eIF2a-P involved induced expression of CDKN1A encoding p21 protein. p21 is a major regulator of the cell cycle, and we show that human CDKN1A mRNA splice variant 4 is preferentially translated by eIF2a-P during stress in a mechanism mediated in part by upstream ORFs situated in the 5'-leader of CDKN1A mRNA. We conclude that eIF2a-P is cytoprotective in response to UVB by a mechanism featuring translation of a specific splice variant of CDKN1A that facilitates G1 arrest and subsequent DNA repair. Overall design: Untreated and irradiated N-TERT keratinocytes are split into 3 groups: monosome fraction, polysome fraction, and whole cell lysate. N=3.
Translational control of a human <i>CDKN1A</i> mRNA splice variant regulates the fate of UVB-irradiated human keratinocytes.
Specimen part, Cell line, Treatment, Subject
View SamplesThe purpose of this study was to identify putative downstream targets of the transcription factor ZIC2 in the mouse embryo. The results indicate loss of NODAL pathway expression, consistent with the observed phenotype of right isomerism in heart, lungs and viscera.
A Requirement for Zic2 in the Regulation of Nodal Expression Underlies the Establishment of Left-Sided Identity.
Specimen part
View SamplesThe 6-hydroxydopamine (6OHDA) rat model of parkinsonism is among the first, and most commonly used, animal models of Parkinsons disease. It provides insight into the compensatory changes that occur in the brain after dopamine (DA) neuron degeneration. In order to better define the consequences of substantia nigra DA neuron loss on the neural and glial populations during and following nigrostriatal degeneration, tissue was collected and evaluated from the substantia nigra of 6OHDA or vehicle treated, or nave rats at 1, 2, 4, 6 & 16 weeks.
The longitudinal transcriptomic response of the substantia nigra to intrastriatal 6-hydroxydopamine reveals significant upregulation of regeneration-associated genes.
Sex, Specimen part
View SamplesRationale: Pulmonary arterial hypertension is a common and potentially fatal complication of scleroderma that may involve inflammatory and autoimmune mechanisms. Alterations in the gene expression of peripheral blood mononuclear cells have been previously described in patients with pulmonary arterial hypertension. The ability to identify patients at risk for developing pulmonary hypertension would be clinically beneficial.
Altered immune phenotype in peripheral blood cells of patients with scleroderma-associated pulmonary hypertension.
Sex, Specimen part, Disease, Disease stage
View SamplesPurpose: The goal of this study was to determine the gene expression changes that occur over 7 days in parralyzed muscle in response to isometric contraction elicited by electrical stimulation initiated 4 months after spinal cord injury and to compare such changes to those observed in a normal muscle subjected to overload.
Electrical stimulation modulates Wnt signaling and regulates genes for the motor endplate and calcium binding in muscle of rats with spinal cord transection.
Sex, Specimen part
View SamplesBacillus anthracis, the causative agent of anthrax, secretes three toxin proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). PA is a transporter of LF and EF into host cells by receptor-mediated endocytosis. LF is a metalloprotease that cleaves mitogen-activated protein kinase (MAPK) kinases (MKK), while EF is an adenylate cyclase, which converts ATP to cAMP.
Antiinflammatory cAMP signaling and cell migration genes co-opted by the anthrax bacillus.
No sample metadata fields
View SamplesArabidopsis is a non-host to the biotrophic fungus Blumeria graminis f.sp. hordei (Bgh), effectively hindering Bgh ingress to the epidermal cells by deposition of callosic papillae formations, i.e. penetration resistance. To better understand the transcriptional changes in Arabidopsis towards Bgh, we compared un-inoculated and inoculated wild-type Arabidopsis samples, with those an ATAF1 mutant allele, compromised in penetration resistance. The experiment included sampling of 8 rosettes for each replicate sample from 6-weeks old plants, 12 hrs after inoculation. A total of 12 biolocigal replicates were sampled with three replicates from each of the four blocks (Wild-type, ataf1-1, Bgh, control). ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Michael Krogh Jensen. The equivalent experiment is AT31 at PLEXdb.]
Transcriptional regulation by an NAC (NAM-ATAF1,2-CUC2) transcription factor attenuates ABA signalling for efficient basal defence towards Blumeria graminis f. sp. hordei in Arabidopsis.
No sample metadata fields
View SamplesTo improve our understanding of lncRNA expression in T cells, we used whole genome sequencing (RNA-seq) to identify lncRNAs expressed in human T cells and those selectively expressed in T cells differentiated under TH1, TH2, or TH17 polarizing conditions. The majority of these lineage-specific lncRNAs are co-expressed with lineage-specific protein-coding genes. These lncRNAs are predominantly intragenic with co-expressed protein-coding genes and are transcribed in sense and antisense orientations with approximately equal frequencies. Further, genes encoding TH lineage specific mRNAs are not randomly distributed across the genome but are highly enriched in the genome in genomic regions also containing genes encoding TH lineage-specific lncRNAs. Our analyses also identify a cluster of antisense lncRNAs transcribed from the RAD50 locus that are selectively expressed under TH2 polarizing conditions and co-expressed with IL4, IL5 and IL13 genes. Depletion of these lncRNAs via selective siRNA treatment demonstrates the critical requirement of these lncRNAs for expression of the TH2 cytokines, IL-4, IL-5 and IL-13. Collectively, our analyses identify new lncRNAs expressed in a TH lineage specific manner and identify a critical role for a cluster of lncRNAs for expression of genes encoding TH2 cytokines. Overall design: Human peripheral blood mononuclear cells (PBMC) were cultured under TH1, TH2, and TH17 polarizing conditions. TH1, TH2, and TH17 primary and effector cultures were isolated and poly(A)+ and total RNA sequencing performed.
Expression and functions of long noncoding RNAs during human T helper cell differentiation.
No sample metadata fields
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