RNA-seq in imprinted vs naive Omicron-positive volunteers
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ABSTRACT:
PROVIDER: PRJEB74628 | ENA |
REPOSITORIES: ENA
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Project description:Naive pluripotent epiblast cells of the preimplantation murine embryo and their in vitro counterpart, embryonic stem (ES) cells, have the capacity to give rise to all cells of the adult. Such developmental plasticity is associated with global genome hypomethylation. It is unclear whether genome methylation is dynamically regulated only via differential expression of DNA methyltransferases (DNMTs) and Ten-eleven Translocation (TET) enzymes, which oxidase methylated DNA. Here we show that LIF/Stat3 signalling induces genomic hypomethylation via metabolic reconfiguration. In Stat3-/- ES cells we observed decreased alpha-ketoglutarate (ɑKG) production from reductive Glutamine metabolism, leading to decreased TET activity, increased Dnmt3a/b expression and to a global increase in DNA methylation. Notably, genome methylation is dynamically controlled by simply modulating αKG availability, mitochondrial activity or Stat3 activation in mitochondria, indicating effective crosstalk between metabolism and the epigenome. Stat3-/- ES cells also show increased methylation at Imprinting Control Regions accompanied with differential expression of >50% of imprinted genes. Single-cell transcriptome analysis of Stat3-/- embryos confirmed dysregulated expression of Dnmt3a/b, Tet2, and imprinted genes in vivo. Our results reveal that the LIF/Stat3 signal bridges the metabolic and epigenetic profiles of naive pluripotent cells, ultimately controlling genome methylation and imprinted gene expression. Several imprinted genes regulate cell proliferation and are often misregulated in tumors. Moreover, a wide range of cancers display Stat3-overactivation, raising the possibility that the molecular module we described here is exploited under pathological conditions.
2020-11-26 | PXD020385 | Pride
Project description:Metabolic control of imprinted gene expression in naive pluripotent cells
| PRJNA555434 | ENA
Project description:In this experiment we generated Affymetrix gene expression data for T Follicular Helper (TFH) cells from tonsils of healthy volunteers (4 biological replicates) and naive CD4-positive helper T cells (2 biological replicates). TFH cells provide a model relevant to SLE as TFH operate upstream of the activation of pathogenic autoantibody-producing B cells during the disease. This experiment accompanies promoter capture-C and ATAC-seq experiments on the same cell types.
2019-04-01 | E-MTAB-6637 | biostudies-arrayexpress
Project description:Naive pluripotent epiblast cells of the preimplantation embryo and their in vitro counterpart, naive murine embryonic stem (ES) cells , are characterised by global DNA hypomethylation. This is caused by elevated expression of TETs oxidases and by downregulation of DNA methyltransferases (DNMTs). However, the signal orchestrating such dynamic changes in vitro and in vivo are only partially understood. Here we report that Stat3 induces genomic hypomethylation via metabolic reconfiguration. In Stat3 -/- ES cells we observed reduced alpha-ketoglutarate (ɑKG) production from reductive glutaminolysis. This is accompanied by reduced levels of Tet2 and its product, hydroxy-methyl-cytosine, together with increased Dnmt3a/b expression and methyl-cytosine levels. Notably, genome methylation can be dynamically controlled by simply modulating αKG availability, mitochondrial activity or Stat3 activation. Stat3-/- ES cells show also general increased methylation at Imprinting Control Regions accompanied with differential expression of >60% of imprinted genes. Several of them, including Lin28a, Ndn and Peg10, are normally upregulated during differentiation, and displayed anticipated and enhanced expression in Stat3-/- cells, indicating faster differentiation kinetics. Single-cell transcriptome analysis of Stat3-/- embryos confirmed dysregulated expression of Dnmt3a/b, Tet2, imprinted genes and anticipated expression of differentiation markers. Our results reveal that Stat3 bridges the metabolic and epigenetic profiles of naive pluripotent cells and may be relevant under Stat3-dependent pathological conditions.
2020-11-30 | GSE134450 | GEO
Project description:Genome Wide Association Studies (GWAS) have been successful in yielding >60 loci for Systemic Lupus Erythematosus (SLE). However, it is known that GWAS just reports genomic signals and not necessarily the precise localization of culprit genes, with eQTL efforts only able to infer causality to a minority of such loci. Thus, we sought to carry out physical and direct ‘variant to gene mapping’ by integrating results from high-throughput chromatin conformation capture and ATAC-seq assays. This experiment refers to the ATAC-seq part of our work. To determine informative proxy SNPs for each of the SLE GWAS sentinel loci, we generated ATAC-seq open chromatin maps for primary human T Follicular Helper (TFH) cells from tonsils of healthy volunteers (3 biological replicates), a model relevant to SLE as TFH operate upstream of the activation of pathogenic autoantibody-producing B cells during the disease. We also generated open chromatin maps for naive CD4-positive helper T cells (3 biological replicates).
2020-05-12 | E-MTAB-6617 | biostudies-arrayexpress
Project description:The COVID-19 pandemic was marked by successive waves of SARS-CoV-2 variants with distinct properties. The Omicron variant that emerged in late 2021 showed a major antigenic shift and rapidly spread worldwide. Since then, Omicron-derived variants have maintained their global dominance, for reasons that remain incompletely understood. We report that the original Omicron variant BA.1 evolved several traits that converged in facilitating viral spread. First, Omicron displayed an early replicative advantage over previous variants when grown in a reconstructed nasal epithelium model based on primary human cells. The increase in Omicron replication was more marked at the 33°C temperature characteristic of human nasal passages, resulting in a physiologically relevant advantage. Omicron also caused a decrease in epithelial integrity, as measured by transepithelial electrical resistance and caspase-3 activation. Furthermore, Omicron caused a more marked loss of motile cilia at 33°C than other variants, suggesting a capacity to impair mucociliary clearance. RNAseq analysis showed that Omicron induced a broad transcriptional downregulation of ciliary genes but only a limited upregulation of host innate defense genes at 33°C. The lower production of type I and type III interferons in epithelia infected by Omicron compared to those infected by the Delta variant, at 33°C as well as 37°C, confirmed the increased capacity of Omicron to evade the innate antiviral response. Thus, Omicron combined replication speed, motile cilia impairment, and limited induction of innate antiviral responses when propagated in reconstructed nasal epithelia at physiological temperature. Omicron has the capacity to propagate efficiently but stealthily in the upper respiratory tract, which likely contributed to the evolutionary success of this SARS-CoV-2 variant.
2025-12-13 | GSE295759 | GEO
Project description:To gain a deeper understanding of Omicron waves in the context of vaccination, we performed scRNA-seq together with single-cell V(D)J sequencing using PBMCs from nine Omicron breakthrough infection patients and six vaccinees to identify the possible cellular and molecular response mechanisms after breakthrough infection.
2024-12-18 | GSE248556 | GEO
Project description:The Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in November 2021 in South Africa, has initiated the 5th wave of global pandemics. Here, we systemically examined immunological and metabolic characteristics of Omicron variants infection. We found Omicron resisted to neutralizing antibody targeting receptor binding domain (RBD) of wild-type SARS-CoV-2. Omicron could not be neutralized by sera of Corona Virus Disease 2019 (COVID-19) convalescent individuals who were infected with the Delta variant. Through mass spectrometry on MHC-bound peptidomes, we found that the spike protein of the Omicron variants could generate additional CD8+ T cell epitopes, compared with Delta. These epitopes could induce robust CD8+ T cell responses. Moreover, we found booster vaccination increased the cross-memory CD8+ T cell responses against Omicron. Metabolic regulome analysis of Omicron-specific T cell showed a metabolic profile that promoted memory T cell responses. Consistently, a higher fraction of memory CD8+ T cells were found in Omicron stimulated peripheral blood mononuclear cells (PBMCs). In addition, CD147 was also a receptor for the Omicron variants, and CD147 antibody inhibited infection of Omicron. CD147-mediated Omicron infection in a human CD147 transgenic mouse model induced exudative alveolar pneumonia. Taken together, our data suggested that vaccination booster and receptor blocking antibody are two effective strategies against Omicron.
2023-03-11 | PXD037955 | Pride
Project description:Antibody response following Omicron infection is reported to be less robust than that to other variants. Here we investigated how prior vaccination and/or prior infection modulates that response. Disease severity, antibody responses and immune transcriptomes were characterized in four groups of Omicron-infected outpatients (n=83): unvaccinated/no prior infection, vaccinated/no prior infection, unvaccinated/prior infection and vaccinated/prior infection. The percentage of patients with asymptomatic or mild disease was highest in the vaccinated/no prior infection group (87%) and lowest in the unvaccinated/no prior infection group (47%). Significant anti-Omicron spike antibody levels and neutralizing activity were detected in the vaccinated group immediately after infection but were not present in the unvaccinated/no prior infection group. Within two weeks, antibody levels against Omicron, increased. Omicron neutralizing activity in the vaccinated group exceeded that of the prior infection group. No increase in neutralizing activity in the unvaccinated/no prior infection group was seen. The unvaccinated/prior infection group showed an intermediate response. We then investigated the early transcriptomic response following Omicron infection in these outpatient populations and compared it to that found in unvaccinated hospitalized patients with Alpha infection. Omicron infected patients showed a gradient of transcriptional response dependent upon whether or not they were previously vaccinated or infected. Vaccinated patients showed a significantly blunted interferon response as compared to both unvaccinated Omicron infected outpatients and unvaccinated Alpha infected hospitalized patients typified by the response of specific gene classes such as OAS and IFIT that control anti-viral responses and IFI27, a predictor of disease outcome.
2022-06-11 | GSE201530 | GEO
Project description:naive T vs conA treated sample
| PRJNA950948 | ENA