To obtain insight into the genetic basis of the increase of functional activity of memory B cells over time, we compared the gene expression profiles of day 7 and day 40 NP-specific/IgG1 memory B cells, GC B cells and plasma cells in immunized WT mice and nave B cells, before and after activation in vitro.
Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory.
Sex, Age, Specimen part
View SamplesBcl6 germline deletion causes a prominent inflammatory disease, owing to over-expression of Th2 cytokines, and affects the properties of B cells prior to immunization. Therefore we established the B cell-specific Bcl6 deletion mice and analyze the gene expression of naive B cells under physiological conditions.
Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory.
Sex, Age
View SamplesPTIP (Pax2 transactivation domain-interacting protein) is a nuclear protein containing six BRCT domains. It has been shown that PTIP affects gene expression by controlling the activity of the transcription factor Pax2 and histone H3 lysine 4 methyltransferase complexes. In addition to its role in transcriptional regulation, PTIP has been implicated in DNA damage response. To ask if the depletion of PTIP affects the expression level of genes encoding DNA damage response factors , we compared the whole transcripts between wild-type and PTIP deficient chicken DT40 B cell lines.
PTIP promotes DNA double-strand break repair through homologous recombination.
Specimen part, Cell line
View SamplesThe development of T cells has been characterized as taking place over three stages: nave (Tn), central memory (Tcm), and effector memory (Tem) cells.
Polarization diversity of human CD4+ stem cell memory T cells.
Sex, Age
View SamplesGrowing evidences are suggesting that extra-long genes in mammals are vulnerable for full-gene length transcription and dysregulation of long genes is a mechanism underlying human genetic disorders. Skeletal muscle expresses Dystrophin which is 2.26 Mbp in length; however, how long-distance transcription is achieved is totally unknown. We had discovered RNA-binding protein SFPQ preferentially binds to long pre-mRNAs and specifically regulates the cluster of neuronal genes > 100 kbp. Here we investigated the roles of SFPQ for long gene expression, target specificities, and also physiological functions in skeletal muscle. Loss of Sfpq selectively downregulated genes >100 kbp including Dystrophin and caused progressive muscle mass reduction and metabolic myopathy characterized by glycogen accumulation and decreased abundance of mitochondrial oxidative phosphorylation complexes. Functional clustering analysis identified metabolic pathway related genes as the targets of SFPQ. These findings indicate target gene specificities and tissue-specific physiological functions of SFPQ in skeletal muscle. Overall design: We analyzed polyA-tailed RNA profiles including transcribing RNAs in gastrocnemius skeletal muscle ( from 3 control and 3 Sfpq-/- P35 male mice) using Ion-proton.
Loss of RNA-Binding Protein Sfpq Causes Long-Gene Transcriptopathy in Skeletal Muscle and Severe Muscle Mass Reduction with Metabolic Myopathy.
Sex, Specimen part, Cell line, Subject
View SamplesGrowing evidences are suggesting that extra-long genes in mammals are vulnerable for full-gene length transcription and dysregulation of long genes is a mechanism underlying human genetic disorders. Skeletal muscle expresses Dystrophin which is 2.26 Mbp in length; however, how long-distance transcription is achieved is totally unknown. We had discovered RNA-binding protein SFPQ preferentially binds to long pre-mRNAs and specifically regulates the cluster of neuronal genes > 100 kbp. Here we investigated the roles of SFPQ for long gene expression, target specificities, and also physiological functions in skeletal muscle. Loss of Sfpq selectively downregulated genes >100 kbp including Dystrophin and caused progressive muscle mass reduction and metabolic myopathy characterized by glycogen accumulation and decreased abundance of mitochondrial oxidative phosphorylation complexes. Functional clustering analysis identified metabolic pathway related genes as the targets of SFPQ. These findings indicate target gene specificities and tissue-specific physiological functions of SFPQ in skeletal muscle. Overall design: We analyzed rRNA-depleted RNA profiles including transcribing RNAs in primary myoblasts obtained from skeletal muscles of 1-month-old SfpqSM-KO (n=1) and control (n=1) mice under differentiated condition using Ion-proton.
Loss of RNA-Binding Protein Sfpq Causes Long-Gene Transcriptopathy in Skeletal Muscle and Severe Muscle Mass Reduction with Metabolic Myopathy.
Subject
View SamplesTrib1 is critical for some myeloid cell differentiation.
Critical role of Trib1 in differentiation of tissue-resident M2-like macrophages.
Specimen part
View SamplesVirus infection induces T follicular helper (TFH) and T helper 1 (TH1) cells. Although TFH cells are important in anti-viral humoral immunity, the role of TH 1 cells is still elusive. IgG2 antibodies predominate in the response to vaccination with inactivated Influenza A virus (IAV) and were responsible for protective immunity to lethal challenge with pathogenic H5N1 and pandemic H1N1 IAVs even in mice lacking TFH cells owing to B or T cell-specific ablation of the Bcl6. We demonstrate that IL-21 and IFN-? secreted from TH1 cells were essential for greater persistence and higher titers of IgG2 protective antibodies. These results suggest that TH1 induction could be a promising strategy to induce effective neutralizing antibodies against emerging influenza viruses. Overall design: TH1 or TFH cells of wild type (WT) and conditional Bcl6-/- mice were sorted and analyzed the transcriptome using Illumina HiSeq1500.
Protective neutralizing influenza antibody response in the absence of T follicular helper cells.
Age, Specimen part, Cell line, Subject
View SamplesWe collected and compared samples from the cohort consisted of six groups as follows: methotrexate (MTX) monotherapy, combination therapy of MTX and infliximab (IFX), tocilizumab (TCZ) monotherapy, age- and gender-matched HC, and a small number of synovial fluid samples. In order to reduce variation due to the proportion of cells at each developmental stage, we performed transcriptome analysis after sorting CD4+ and CD8+ T cells according to developmental stage. We created a gene list that was significantly expressed in RA T cells, and revealed that pathways such as mTORC1, IL-2-stat5, Cell cycle and interferon-related genes were significantly enriched among them. Overall design: Examination among healthy controls and patients with rheumatoid arthritis, including before and after treatment
Multi-dimensional analysis identified rheumatoid arthritis-driving pathway in human T cell.
Sex, Age, Specimen part, Disease, Subject
View SamplesWe compared whole CD4+ and CD8+ T cells from frozen PBMC samples that were collected before and after treatment initiation of each patient with rheumatoid arthritis. Lists consisting of 858 and 950 differentially expressed genes were created from CD4 and CD8, respectively, and these were used for enrichment analysis. As a result, we found that certain pathways were downregulated after TCZ treatment in both CD4+ and CD8+ T cells, including mechanistic target of rapamycin complex 1 (mTORC1) signaling, the IL-2 pathway, and IFN-related genes. Overall design: Examination between before and after tocilizumab treatment of CD4 and CD8 T cell in rheumatoid arthritis patients
Multi-dimensional analysis identified rheumatoid arthritis-driving pathway in human T cell.
Sex, Age, Specimen part, Disease, Subject
View Samples