Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-75111E-GEOD-75105E-GEOD-75104E-GEOD-75106E-GEOD-75107E-GEOD-75103E-GEOD-75108E-GEOD-75110E-GEOD-75109
PROVIDER: PRJNA302464 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Extensive cellular heterogeneity exists within specific immune-cell subtypes classified as a single lineage, but its molecular underpinnings are rarely characterized at a genomic scale. Here, we use single-cell RNA-seq to investigate the molecular mechanisms governing heterogeneity and pathogenicity of Th17 cells isolated from the central nervous system (CNS) and lymph nodes (LN) at the peak of autoimmune encephalomyelitis (EAE) or polarized in vitro under either pathogenic or non-pathogenic differentiation conditions. Computational analysis reveals a spectrum of cellular states in vivo, including a self-renewal state, Th1-like effector/memory states and a dysfunctional/senescent state. Relating these states to in vitro differentiated Th17 cells, unveils genes governing pathogenicity and disease susceptibility. Using knockout mice, we validate four novel genes: Gpr65, Plzp, Toso and Cd5l (in a companion paper). Cellular heterogeneity thus informs Th17 function in autoimmunity, and can identify targets for selective suppression of pathogenic Th17 cells while sparing non-pathogenic tissue-protective ones. Population transcriptional profiling of KO or WT cells,, differentiated in vitro for 48-96h towards Th17 cells
| E-GEOD-75104 | BioStudies
Project description:Extensive cellular heterogeneity exists within specific immune-cell subtypes classified as a single lineage, but its molecular underpinnings are rarely characterized at a genomic scale. Here, we use single-cell RNA-seq to investigate the molecular mechanisms governing heterogeneity and pathogenicity of Th17 cells isolated from the central nervous system (CNS) and lymph nodes (LN) at the peak of autoimmune encephalomyelitis (EAE) or polarized in vitro under either pathogenic or non-pathogenic differentiation conditions. Computational analysis reveals a spectrum of cellular states in vivo, including a self-renewal state, Th1-like effector/memory states and a dysfunctional/senescent state. Relating these states to in vitro differentiated Th17 cells, unveils genes governing pathogenicity and disease susceptibility. Using knockout mice, we validate four novel genes: Gpr65, Plzp, Toso and Cd5l (in a companion paper). Cellular heterogeneity thus informs Th17 function in autoimmunity, and can identify targets for selective suppression of pathogenic Th17 cells while sparing non-pathogenic tissue-protective ones. Population transcriptional profiling of KO or WT cells,, differentiated in vitro for 48-96h towards Th17 cells
2015-11-20 | E-GEOD-75104 | ArrayExpress
Project description:Genome-wide analysis of Jarid2, Suz12, and c-Maf binding and H3K27me3 profiling in miR-155 KO and WT Th17 performed by ChIP-seq. We found that Jarid2 and c-Maf is differentially expressed in absence of miR-155 and they compete for binding to the Il22 promoter. We highlight targets of Jarid2 and Suz12 in miR-155 KO Th17 cells that are epigenetically silenced by increased H3K27me3 status. Furthermore, genome-wide analysis through Suz12 ChIP-exo in WT and Jarid2fl/fl;CD4cre Th17 reveals defects in PRC2 recruitment in abscence of Jarid2 that results in derepression of genes in Th17 cells. Thus, one main function of miR-155 is to curb epigenetic silencing by targeting Jarid2. Examination of Jarid2, Suz12, c-Maf binding and H3K27me3 changes in miR-155 KO and WT Th17.
| E-GEOD-47528 | BioStudies
Project description:Purpose: Characterize the role of the coactivator subunit TAF9b during differentiation of embryonic stem cells into motor neurons as well in mouse newborn spinal column tissues. RNA-seq comparing WT and TAF9B KO mouse ES cells differentiated into motor neurons. RNA-seq comparing WT and TAF9B KO mouse newborn spinal column tissues. ChIP-seq mapping TAF9b and RNA Pol II binding sites in in vitro differentiated motor neurons.
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Project description:Peptidyl arginine deiminase 4 (PAD4) is an enzyme that is involved in protein citrullination, and is a target for anti-citrullinated peptide antibodies (ACPAs) in rheumatoid arthritis (RA). Genetic polymorphisms in the PADI4 gene encoding PAD4 are associated with RA susceptibility. We herein analyzed the roles of PADI4 in inflammatory arthritis using a glucose-6-phosphate isomerase (GPI)-induced arthritis (GIA) model in Padi4 knockout (KO) mice. Arthritis severity, serum anti-GPI antibody titers, and IL-6 concentrations were significantly reduced in Padi4 KO mice. The frequency of Th17 cells was decreased in GPI-immunized Padi4 KO mice, whereas WT and Padi4-deficient naïve CD4(+) T cells displayed the same efficiencies for Th17 cell differentiation in vitro. In addition, the numbers of myeloid lineage cells were reduced with the increased expression of pro-apoptotic genes in GPI-immunized Padi4 KO mice. Furthermore, the survival of Padi4-deficient neutrophils was impaired in vitro. Our results suggest that PADI4 exacerbates arthritis with diverse immunological modifications.
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Project description:Total RNA were extracted from osteoclasts differentiated from RAW264.7 cells at different stages: Monocytes (0h), Pre-osteoclasts (24h), Mature osteoclasts (72h) and activated osteoclasts (96h). LncRNA and mRNA expression profiles were decided by microarray. RAW264.7 cells were cultured with RANKL (100ng/ml) and M-CSF (50ng/ml) for 0h, 24h, 72h and 96h. TRAP stain, FAK stain, pit formation assay, fusion assay and q-PCR were performed to validate the in vitro model.
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Project description:We report here differentiated enrichment of H3K4me1 at Lsh WT and KO mouse embryonic fibroblasts (MEFs). We found a subset of differentially enriched H3K4me1 regions in Lsh KO MEFs, and they clustered at neuronal lineage genes and overlapping with known cis-regulatory elements present in brain tissue. Reprogramming of Lsh?/? MEFs into induced pluripotent stem (iPS) cells leads to increased neuronal lineage gene expression of premarked genes and enhanced differentiation potential of Lsh?/? iPS cells toward the neuronal lineage pathway compared with WT iPS cells in vitro and in vivo. The state of H3K4me1 enrichment is partially maintained in Lsh?/? iPS cells, suggesting the regions are preserved as potential enhancers. Genome-wide maps of H3K4me1 in Lsh WT and KO primary MEFs.
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Project description:The etiology of sarcoidosis is unknown. In this study, <i>Propionibacterium acnes</i> (PA) was used to induce sarcoidosis-like granulomatous inflammation in a mouse model. Wild-Type (WT) C57BL/6 mice were divided into three groups: (1) WT-PA group; (2) WT-PA + Incomplete Freund's Adjuvant (IFA) group; and (3) WT-PBS group. Loose granuloma formation was observed in the lungs on day 56 in the WT-PA and WT-PA + IFA groups. The proportions of peripheral Th17 cells in the WT-PA (<i>p</i> = 0.0004) and WT-PA + IFA groups (<i>p</i> = 0.0005) were significantly higher than that in the WT-PBS group. The proportions of peripheral Treg cells in the WT-PA (<i>p</i> < 0.0001) and WT-PA + IFA groups (<i>p</i> < 0.0001) were lower than that in the WT-PBS group. Then, to explore the mechanism of IL-17, Wild-Type (WT) C57BL/6 mice were divided into three groups: (1) WT-PBS group (2) WT-PA group; (3) WT-PA + mouse IL-17A neutralizing antibody (IL-17Ab) group. IL-17A gene knockout mice (KO) were divided into two groups: (1) KO -PA group; (2) KO-PBS group. The KO-PA and WT-PA + IL-17Ab groups showed reduced inflammation and no loose granuloma formation on day 56. As compared to the WT-PA group, the ratio of peripheral Th17 in the KO-PA (<i>p</i> < 0.0001) and WT-PA + IL-17Ab groups (<i>p</i> < 0.0001) decreased, while the ratio of peripheral Treg in the KO-PA (<i>p</i> < 0.0001) and WT-PA + IL-17Ab (<i>p</i> = 0.0069) groups increased on day 56. Hence, PA can be used to establish a mouse model of sarcoidosis-like granuloma. IL-17A plays an important role in experimental sarcoidosis-like granuloma formation.
| S-EPMC6702313 | BioStudies
Project description:The type III histone deacetylase silent information regulator 1 (SIRT1) is an enzyme that is critical for the modulation of immune and inflammatory responses. However, the data on its role in rheumatoid arthritis (RA) are limited and controversial. To better understand how SIRT1 regulates adaptive immune responses in RA, we evaluated collagen-induced arthritis (CIA) in myeloid cell-specific SIRT1 knockout (mSIRT1 KO) and wild-type (WT) mice. Arthritis severity was gauged on the basis of clinical, radiographic and pathologic scores. Compared with their WT counterparts, the mSIRT1 KO mice exhibited less severe arthritis, which was less destructive to the joints. The expression levels of inflammatory cytokines, matrix metalloproteinases and ROR-?T were also reduced in the mSIRT1 KO mice compared with the WT mice and were paralleled by reductions in the numbers of Th1 and Th17 cells and CD80- or CD86-positive dendritic cells (DCs). In addition, impaired DC maturation and decreases in the Th1/Th17 immune response were observed in the mSIRT1 KO mice. T-cell proliferation was also investigated in co-cultures with antigen-pulsed DCs. In the co-cultures, the DCs from the mSIRT1 KO mice showed decreases in T-cell proliferation and the Th1/Th17 immune response. In this study, myeloid cell-specific deletion of SIRT1 appeared to suppress CIA by modulating DC maturation. Thus, a careful investigation of DC-specific SIRT1 downregulation is needed to gauge the therapeutic utility of agents targeting SIRT1 in RA.
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Project description:Th17 cells are believed to be a critical cell population for driving autoimmune diseases. However, environmental factors that are directly related to the development of Th17 cells are largely unknown. High-salt (NaCl) concentrations enhance Th17 differentiation of human naive CD4+ T cells in vitro. The aim of the study was to analyse the changes in gene expression induced by high-salt conditions during Th17 differentiation. Naive human CD4+ T cells were in vitro differentiated into Th17 cells in the presence or absence of high-salt. We arrayed 2 different donors for each condition (control & high-salt).
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