HM1, HP1a-/-, and HP1b-/- ESC transcriptomes were generated to determine whether depletion of these HP1 proteins influences gene and/or retroelement expression Overall design: mRNA profiles of HP1a and HP1b Knockouts and its corresponding wildtype
Distinct roles of KAP1, HP1 and G9a/GLP in silencing of the two-cell-specific retrotransposon MERVL in mouse ES cells.
Specimen part, Subject
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Stem cells for murine interstitial cells of cajal suppress cellular immunity and colitis via prostaglandin E2 secretion.
Specimen part, Cell line
View SamplesObjective : To study molecular changes in the articular cartilage and subchondral bone of the tibial plateau from mice deficient in frizzled related protein (Frzb) compared to wild-type mice by transcriptome analysis.
Tight regulation of wingless-type signaling in the articular cartilage - subchondral bone biomechanical unit: transcriptomics in Frzb-knockout mice.
Sex, Age, Specimen part
View SamplesDNA methylation and histone H3 lysine 9 trimethylation (H3K9me3) play important roles in silencing of genes and retroelements. However, a comprehensive comparison of genes and repetitive elements repressed by these pathways has not been reported. Here we show that in mouse embryonic stem cells (mESCs), the genes up-regulated following deletion of the H3K9 methyltransferase Setdb1 are distinct from those de-repressed in mESC deficient in the DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b, with the exception of a small number of primarily germline-specific genes. Numerous endogenous retroviruses (ERVs) lose H3K9me3 and are concomitantly de-repressed exclusively in SETDB1 knockout mESCs. Strikingly, ~15% of up-regulated genes are induced in association with de-repression of promoter proximal ERVs, half in the context of "chimaeric" transcripts that initiate within these retroelements and splice to genic exons. Thus, SETDB1 plays a previously unappreciated yet critical role in inhibiting aberrant gene transcription by suppressing the expression of proximal ERVs. Overall design: NChIP-seq and mRNA-seq of WT, SETDB1 KO and DMNT1 TKO mESCs
DNA methylation and SETDB1/H3K9me3 regulate predominantly distinct sets of genes, retroelements, and chimeric transcripts in mESCs.
No sample metadata fields
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Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells.
Specimen part, Treatment, Time
View SamplesDNA methylation is a heritable epigenetic modification involved in gene silencing, imprinting, and the suppression of retrotransposons. Global DNA demethylation occurs in the early embryo and the germline and may be mediated by Tet (ten-eleven-translocation) enzymes, which convert 5-methylcytosine (mC) to 5-hydroxymethylcytosine (hmC). Tet enzymes have been extensively studied in mouse embryonic stem (ES) cells, which are generally cultured in the absence of Vitamin C, a potential co-factor for Fe(II) 2-oxoglutarate dioxygenase enzymes like Tets. Here we report that addition of Vitamin C to ES cells promotes Tet activity leading to a rapid and global increase in hmC. This is followed by DNA demethylation of numerous gene promoters and up-regulation of demethylated germline genes. Tet1 binding is enriched near the transcription start site (TSS) of genes affected by Vitamin C treatment. Importantly, Vitamin C, but not other antioxidants, enhances the activity of recombinant human Tet1 in a biochemical assay and the Vitamin C-induced changes in hmC and mC are entirely suppressed in Tet1/2 double knockout (Tet DKO) ES cells. Vitamin C has the strongest effects on regions that gain methylation in cultured ES cells compared to blastocysts and in vivo are methylated only after implantation. In contrast, imprinted regions and intracisternal A-particle (IAP) elements, which are resistant to demethylation in the early embryo, are resistant to Vitamin C-induced DNA demethylation. Collectively, this study establishes that Vitamin C is a direct regulator of Tet activity and DNA methylation fidelity in ES cells.
Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells.
Specimen part
View SamplesRheumatoid arthritis (RA) is an inflammatory joint disorder that results in progressive joint damage when insufficiently treated. In order to prevent joint destruction and functional disability in RA, early diagnosis and initiation of appropriate treatment with Disease-Modifying Antirheumatic Drugs (DMARDs) is needed. However, in daily clinical practice, patients may initially display symptoms of arthritis that do not fulfil the classification criteria for a definite diagnosis of RA, or any other joint disease, a situation called Undifferentiated Arthritis (UA). Out of the patients with UA, 30 to 50% usually develop RA, and early identification of these remains a challenge.
Identification of distinct gene expression profiles in the synovium of patients with systemic lupus erythematosus.
Sex, Age, Specimen part, Disease, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells.
Sex, Specimen part, Cell line
View SamplesWe surveyed RNA-Seq data to identify those TEs that are transcriptionally active uniquely in human pluripotent cells. We identified one endogenous retrovirus (HERV-H) family, uniquely found in primates as being unusually abundant in the transcriptome. The microarray data provided is to support our human naive cell hypothesis.
Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells.
Sex, Cell line
View SamplesObjective: Rituximab displays therapeutic benefits in the treatment of rheumatoid arthritis (RA) patients resistant to TNF blockade. However, the precise role of B cells in the pathogenesis of RA is still unknown. In this study we investigated the global molecular effects of rituximab in synovial biopsies obtained from anti-TNF resistant RA patients before and after administration of the drug.
Rituximab treatment induces the expression of genes involved in healing processes in the rheumatoid arthritis synovium.
Sex, Specimen part, Disease, Disease stage, Treatment
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