During early development before gonadal differentiation, sex chromosomes are the main difference between males and females. We examined any genetically driven sex dimorphisms in human pluripotent stem cells focusing on Y chromosome contribution.
Sex-dependent gene expression in human pluripotent stem cells.
Sex, Specimen part
View SamplesGATA transcription factors are highly conserved among eukaryotes and play roles in transcription of genes implicated in cancer progression and hematopoiesis. However, although their consensus binding sites have been well defined in vitro, the in vivo selectivity for recognition by GATA factors remains poorly characterized. Using ChIP-Seq, we identified the Dal80 GATA factor targets in yeast. Our data reveal Dal80 binding to a large set of promoters, sometimes independently of GATA sites, correlating with nitrogen- and/or Dal80-sensitive gene expression. Strikingly, Dal80 was also detected across the body of promoter-bound genes, correlating with high expression. Mechanistic single-gene experiments showed that Dal80 spreading across gene bodies requires active transcription. Consistently, Dal80 co-immunoprecipitated with the initiating and post-initiation forms of RNA Polymerase II. Our work suggests that GATA factors could play dual, synergistic roles during transcription initiation and post-initiation steps, promoting efficient remodeling of the gene expression program in response to environmental changes. Overall design: Strand-specific total RNA-Seq analysis in wild-type (WT) and dal80-delta (dal80) cells grown in glutamine- and/or proline-containing medium.
Transcription-dependent spreading of the Dal80 yeast GATA factor across the body of highly expressed genes.
Subject
View SamplesDevelopmentally synchronized animals were obtained by hypochlorite treatment of gravid adults to release embryos. Synchronized embryos were hatched on NGM plates and grown at 20°C until 48 h after the L4 stage of development. Fluorodeoxyuridine was used to prevent the development of second-generation embryos once animals reached fertile adulthood. For each RNA-seq experiment, populations for odIs77[Pcol-19::UbG76V-GFP] and dop-1(vs100); [Pcol- 19::UbG76V-GFP] were grown simultaneously under the same conditions. Total RNA was isolated from animals using trizol (Invitrogen) combined with Bead Beater lysis in 3 biological replicates, and an mRNA library (single-end, 50-bp reads) was prepared for each sample/replicate using Illumina Truseq with PolyA selection. Overall design: Examination of mRNA levels in adults dop-1 mutants and wild-type animals.
Dopamine signaling promotes the xenobiotic stress response and protein homeostasis.
Specimen part, Subject
View SamplesEmbryonic fibroblast from C57BL/6 (B6) mice were reprogrammed to EiPS without exogenous DNA integration using an single episomal vector. The EiPS cells and B6 ES cells were then transplanted into B6 mice to form teratomas.
Immunogenicity of induced pluripotent stem cells.
No sample metadata fields
View SamplesSignaling by the cytokine LIF and its downstream transcription factor, STAT3, prevents differentiation of pluripotent embryonic stem cells (ESCs) by opposing MAP kinase signaling. This contrasts with most cell types where STAT3 signaling induces differentiation. We find that STAT3 binding across the pluripotent genome is dependent upon Brg, the ATPase subunit of a specialized chromatin remodeling complex (esBAF) found in ESCs. Brg is required to establish chromatin accessibility at STAT3 binding targets, in essence preparing these sites to respond to LIF signaling. Moreover, Brg deletion leads to rapid Polycomb (PcG) binding and H3K27me3-mediated silencing of many Brg-activated targets genome-wide, including the target genes of the LIF signaling pathway. Hence, one crucial role of Brg in ESCs involves its ability to potentiate LIF signaling by opposing PcG. Contrary to expectations, Brg also facilitates PcG function at classical PcG target including all four Hox loci, reinforcing their repression in ESCs. These findings reveal that esBAF does not simply antagonize PcG, but rather, the two chromatin regulators act both antagonistically and synergistically with the common goal of supporting pluripotency.
esBAF facilitates pluripotency by conditioning the genome for LIF/STAT3 signalling and by regulating polycomb function.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
In Silico Characterization of miRNA and Long Non-Coding RNA Interplay in Multiple Myeloma.
Specimen part, Disease
View SamplesThe identification of deregulated microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in multiple myeloma (MM) has progressively added a further level of complexity to MM biology. In addition, the cross-regulation between lncRNAs and miRNAs has begun to emerge, and theoretical and experimental studies have demonstrated the competing endogenous RNAs (ceRNAs) activity of lncRNAs as natural miRNA decoys in pathophysiological conditions, including cancer. Currently, information concerning lncRNA and miRNA interplay in MM is virtually absent. Herein, we investigated in silico the lncRNA and miRNA relationship in a representative datasets encompassing 95 MM and 30 plasma cell leukemia patients at diagnosis and in four normal controls, whose expression profiles were generated by a custom annotation pipeline to detect specific lncRNAs. We applied target prediction analysis based on miRanda and RNA22 algorithms to 235 lncRNAs and 459 miRNAs selected with a potential pivotal role in the pathology of MM. Among pairs that showed significant correlation between lncRNA and miRNA expression levels, we identified 10 lncRNA-miRNA relationships suggestive of novel ceRNA network with relevance in MM.
In Silico Characterization of miRNA and Long Non-Coding RNA Interplay in Multiple Myeloma.
Specimen part, Disease
View SamplesThe identification of deregulated microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in multiple myeloma (MM) has progressively added a further level of complexity to MM biology. In addition, the cross-regulation between lncRNAs and miRNAs has begun to emerge, and theoretical and experimental studies have demonstrated the competing endogenous RNAs (ceRNAs) activity of lncRNAs as natural miRNA decoys in pathophysiological conditions, including cancer. Currently, information concerning lncRNA and miRNA interplay in MM is virtually absent. Herein, we investigated in silico the lncRNA and miRNA relationship in a representative datasets encompassing 95 MM and 30 plasma cell leukemia patients at diagnosis and in four normal controls, whose expression profiles were generated by a custom annotation pipeline to detect specific lncRNAs. We applied target prediction analysis based on miRanda and RNA22 algorithms to 235 lncRNAs and 459 miRNAs selected with a potential pivotal role in the pathology of MM. Among pairs that showed significant correlation between lncRNA and miRNA expression levels, we identified 10 lncRNA-miRNA relationships suggestive of novel ceRNA network with relevance in MM.
In Silico Characterization of miRNA and Long Non-Coding RNA Interplay in Multiple Myeloma.
Specimen part, Disease
View SamplesTemperature, as a universal enviromental factor, has prolonged effect on physiological and pathological functions of different species. In order to expolore the temperol effect of temperature on C.elegans longevity, we used microarray to check the whole-genome expression profiling of L4 larvae and Day3-old adults of C.elegans maintaining at different temperature
Environmental Temperature Differentially Modulates C. elegans Longevity through a Thermosensitive TRP Channel.
Treatment
View SamplesEndoplasmic reticulum (ER) thiol oxidases initiate a disulfide relay to oxidatively-fold secreted proteins. We found that combined loss-of-function mutations in genes encoding the ER thiol oxidases ERO1alpha, ERO1beta and PRDX4, compromised the extracellular matrix in mice and interfered with the intracellular maturation of procollagen. These severe abnormalities were associated with an unexpectedly-modest delay in disulfide bond formation in secreted proteins but a profound, five-fold lower procollagen 4 hydroxyproline content and enhanced cysteinyl sulfenic acid modification of ER proteins. Tissue ascorbic acid content was lower in mutant mice and ascorbic acid supplementation improved procollagen maturation and lowered sulfenic acid content, in vivo. In vitro, the presence of a sulfenic acid donor accelerated the oxidative inactivation of ascorbate by an H2O2 generating system. Compromised ER disulfide relay thus exposes protein thiols to competing oxidation to sulfenic acid, resulting in depletion of ascorbic acid, impaired procollagen proline 4-hydroxylation and a non-canonical form of scurvy.
Endoplasmic reticulum thiol oxidase deficiency leads to ascorbic acid depletion and noncanonical scurvy in mice.
Specimen part
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