Histone H3 lysine 9 (H3K9) methylation is an epigenetic mark of transcriptionally repressed chromatin. During mammalian development, H3K9 methylation levels seem to be spatiotemporally regulated by the opposing activities of methyltransferases and demethylases to govern correct gene expression. However, the combination(s) of H3K9 methyltransferase(s) and demethylase(s) that contribute to this regulation and the genes regulated by them remain unclear. Herein, we demonstrate the essential roles of H3K9 demethylases Jmjd1a and Jmjd1b in the embryogenesis and viability control of embryonic stem (ES) cells. Mouse embryos lacking Jmjd1a/Jmjd1b died after implantation. Depletion of Jmjd1a/Jmjd1b in mouse ES cells induced rapid cell death accompanied with a massive increase in H3K9 methylation. Jmjd1a/Jmjd1b depletion induced an increase in H3K9 methylation in the gene-rich regions of the chromosomes, indicating that Jmjd1a/Jmjd1b removes H3K9 methylation marks in the euchromatin. Importantly, the additional disruption of the H3K9 methyltransferase G9a in a Jmjd1a/Jmjd1b-deficient background rescued not only the H3K9 hypermethylation phenotype but also the cell death phenotype. We also found that Jmjd1a/Jmjd1b removes H3K9 methylation marks deposited by G9a in the Oct4 and Ccnd1 loci to activate transcription. In conclusion, Jmjd1a/Jmjd1b ensures ES cell viability by antagonizing G9a-mediated H3K9 hypermethylation in the gene-rich euchromatin.
Combined Loss of JMJD1A and JMJD1B Reveals Critical Roles for H3K9 Demethylation in the Maintenance of Embryonic Stem Cells and Early Embryogenesis.
Specimen part
View SamplesWe established two clones of induced pluripotent stem cells (iPSC) with the presenilin 2 mutation, N141 (PS2-1 iPSC and PS2-2 iPSC) by retroviral transduction of primary human fibroblasts. To show the similarity among 201B7 iPSC, PD01-25 iPSC(Sporadic Parkinson's disease patient derived iPSC), PS2-1 iPSC, PS2-2 iPSC, this experiment was designed.
Modeling familial Alzheimer's disease with induced pluripotent stem cells.
Specimen part, Disease, Disease stage, Cell line
View SamplesBackgroundAcute coronary syndrome (ACS) is sometimes accompanied by accelerated coagulability, lipid metabolism, and inflammatory responses, which are not attributable to the cardiac events alone. We hypothesized that the liver plays a pivotal role in the pathophysiology of ACS. We simultaneously analyzed the gene expression profiles of the liver and heart during acute myocardial ischemia in mice.
Altered hepatic gene expression profiles associated with myocardial ischemia.
Sex, Specimen part
View SamplesGene expression profiling was performed on biopsies of affected and unaffected psoriatic skin and normal skin from seven Japanese patients to obtain insights into the pathways that control this disease. U95A Affymetrix DNA chips that contain oligonucleotide arrays of approximately 12,000 well-characterized human genes were used in the study. The statistical analysis of the Affymetrix data, based on the ranking of the Student-test statistic, revealed a complex regulation of molecular stress and immune gene responses. The majority of the 266 induced-genes in affected and unaffected psoriatic skin were involved with interferon mediation, immunity, cell-adhesion, cytoskeleton restructuring, protein trafficking and degradation, RNA regulation and degradation, signaling transduction, apoptosis and atypical epidermal cellular proliferation and differentiation. The disturbances in the normal protein degradation equilibrium of skin were reflected by the significant increase in the gene expression of various protease inhibitors and proteinases including the induced components of the ATP/ubiquitin-dependent non-lysosomal proteolytic pathway that is involved with peptide processing and presentation to T-cells. Some of the upregulated genes, such as TGM1, IVL, CSTA, FABP5 and SPRR, are well known psoriatic markers involved in atypical epidermal cellular organization and differentiation. In the comparison between the affected and unaffected psoriatic skin, the transcription factor JUNB was found at the top of the statistical rankings for the 51 significantly upregulated genes in affected skin, suggesting that it has an important but as yet undefined role in psoriasis. Our gene expression data and analysis suggest that psoriasis is a chronic IFN and T-cell-mediated immune disease of the skin where the imbalance in epidermal cellular structure, growth and differentiation arises from the molecular antiviral stress signals initiating inappropriate immune responses.
Gene expression profiling of Japanese psoriatic skin reveals an increased activity in molecular stress and immune response signals.
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View SamplesMemory helper T cells provide long-lasting host defeMemory helper T cells provide long-lasting host defense against microbial pathogens, while distinct subpopulations of memory T cells drive chronic inflammatory diseases such as asthma. Asthma is a chronic allergic inflammatory disease with airway remodeling including fibrotic changes. The immunological mechanisms that induce airway fibrotic changes in allergic inflammation remain unknown. We found that Interleukin-33 (IL-33) enhanced Amphiregulin production by the IL-33 receptor, ST2hi memory T helper-2 (Th2) cells. Amphiregulin-epidermal growth factor receptor (EGFR)-mediated signaling directly reprogramed eosinophils to an inflammatory state with enhanced production of Osteopontin, a key profibrotic immunomodulatory protein. IL-5-producing memory Th2 cells and Amphiregulin-producing memory Th2 cells appeared to cooperate to establish lung fibrosis. The analysis of polyps from patients with eosinophilic chronic rhinosinusitis revealed fibrosis with accumulation of Amphiregulin-producing CRTH2hiCD161hiCD45RO+CD4+ Th2 cells and Osteopontin-producing eosinophils. Thus, the IL-33-Amphiregulin-Osteopontin axis directs fibrotic responses in eosinophilic airway inflammation and is a potential target for the treatment of fibrosis induced by chronic allergic disorders. against microbial pathogens, while distinct subpopulations of memory T cells drive chronic inflammatory diseases such as asthma. Asthma is a chronic allergic inflammatory disease with airway remodeling including fibrotic changes. The immunological mechanisms that induce airway fibrotic changes in allergic inflammation remain unknown. We found that Interleukin-33 (IL-33) enhanced Amphiregulin production by the IL-33 receptor, ST2Â hi memory T helper-2 (Th2) cells. Amphiregulin-epidermal growth factor receptor (EGFR)-mediated signaling directly reprogramed eosinophils to an inflammatory state with enhanced production of Osteopontin, a key profibrotic immunomodulatory protein. IL-5-producing memory Th2 cells and Amphiregulin-producing memory Th2 cells appeared to cooperate to establish lung fibrosis. The analysis of polyps from patients with eosinophilic chronic rhinosinusitis revealed fibrosis with accumulation of Amphiregulin-producing CRTH2hiCD161hiCD45RO+CD4+ Th2 cells and Osteopontin-producing eosinophils. Thus, the IL-33-Amphiregulin-Osteopontin axis directs fibrotic responses in eosinophilic airway inflammation and is a potential target for the treatment of fibrosis induced by chronic allergic disorders. Overall design: Amphiregulin producing cells, eosinophils and lung treated with HDM are assessed by RNA-seq.
Amphiregulin-Producing Pathogenic Memory T Helper 2 Cells Instruct Eosinophils to Secrete Osteopontin and Facilitate Airway Fibrosis.
Specimen part, Cell line, Subject
View SamplesWe established induced pluripotent stem cells (iPSC) from centrenarians by retroviral transduction of primary human fibroblasts. To show the similarity between 201B7 iPSC and 100-1 #16 iPSC (induced pluripotent stem cells from centenarian), this experiment was designed.
Establishment of induced pluripotent stem cells from centenarians for neurodegenerative disease research.
Specimen part, Cell line
View SamplesWe explored Max ablation-mediated up-regulation of germ-related genes, especially meiosis-related genes in mouse embryonic stem cells which were cultured either under conventional mouse ES medium or 2i condition using inhibitors against MEK and GSK3b.
Loss of MAX results in meiotic entry in mouse embryonic and germline stem cells.
Sex, Specimen part
View SamplesSo far, we have found PMA induced USP2b isoform in myeloid leukemia cell lines such as HL60, THP-1, and U937.
Ubiquitin-specific protease 2-69 in macrophages potentially modulates metainflammation.
Treatment
View SamplesMyeloid leukemia cell lines HL60, THP-1, and U937 undergo macrophage-like differentiation after treatment with phorbol ester.
Ubiquitin-specific protease 2-69 in macrophages potentially modulates metainflammation.
Cell line, Time
View SamplesTo assess RNA regulation in FALS for gene expression and alternative processing of RNA in the motor neuron precurssors (MPCs)
Establishment of In Vitro FUS-Associated Familial Amyotrophic Lateral Sclerosis Model Using Human Induced Pluripotent Stem Cells.
Specimen part
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