TGF-b is an important pleiotropic cytokine with potent immunoregulatory properties. Although many previous reports have been proposed for the immunoregulatory functions of TGF-b on T cells, such as the suppression of cell proliferation, cytokine production and cytokine signaling, as well as the induction of apoptosis, it is not well elucidated whether the each effect of TGF-b on T cells is dependent on Smad signaling or Smad-independent other signaling pathways.
Smad2 and Smad3 are redundantly essential for the TGF-beta-mediated regulation of regulatory T plasticity and Th1 development.
Specimen part, Treatment
View SamplesPatients with metastatic colorectal cancer were enrolled for treatment with cetuximab monotherapy. Transcriptional profiling was conducted on RNA from pre-treatment metastatic site biopsies to identify genes whose expression correlates with best clinical responses.
Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab.
Specimen part
View SamplesRigosertib treatment of head and neck squamous cell cancer
The dual pathway inhibitor rigosertib is effective in direct patient tumor xenografts of head and neck squamous cell carcinomas.
Specimen part, Cell line
View SamplesPressure overload induces a transition from cardiac hypertrophy to heart failure, but its underlying mechanisms remain elusive. Here we reconstruct a trajectory of cardiomyocyte remodeling and clarify distinct cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure, by integrating single-cardiomyocyte transcriptome with cell morphology, epigenomic state and heart function. During early hypertrophy, cardiomyocytes activate mitochondrial translation/metabolism genes, whose expression is correlated with cell size and linked to ERK1/2 and NRF1/2 transcriptional networks. Persistent overload leads to a bifurcation into adaptive and failing cardiomyocytes, and p53 signaling is specifically activated in late hypertrophy. Cardiomyocyte-specific p53 deletion shows that cardiomyocyte remodeling is initiated by p53-independent mitochondrial activation and morphological hypertrophy, followed by p53-dependent mitochondrial inhibition, morphological elongation, and heart failure gene program activation. Human single-cardiomyocyte analysis validates the conservation of the pathogenic transcriptional signatures. Collectively, cardiomyocyte identity is encoded in transcriptional programs that orchestrate morphological and functional phenotypes. Overall design: Integrative analysis of single-cardiomyocyte RNA-seq of pressure-overload-induced heart failure model mice and heart failure patients with dilated cardiomyopathy, single-cell morphology, cardiac function and genetic perturbation
Cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure.
Subject
View SamplesThe goal of this study is to evaluate immune profile in anti PD-1 antibody, Nivolumab, bound CD8 T cells vs Nivolumab unbound CD8 T cells. Overall design: We performed sorting for IgG4 positive and negative CD8 T cells from five individual patients at the time after one dose treatment and compared transcriptome profile between them.
Clinical implications of monitoring nivolumab immunokinetics in non-small cell lung cancer patients.
Specimen part, Subject
View SamplesEffector CD8+ T cells are believed to be terminally differentiated cells having cytotoxic activity and the ability to produce effector cytokines such as INF- and TNF-. We investigated the difference between CXCR1+ and CXCR1- subsets of human effector CD27-CD28-CD8+ T cells. Both subsets similarly expressed cytolytic molecules and exerted substantial cytolytic activity, whereas only the CXCR1- subset had IL-2 productivity and self-proliferative activity and was more resistant to cell death than the CXCR1+ subset. These differences were explained by the specific up-regulation of CAMK4, SPRY2, and IL-7R in the CXCR1- subset and that of pro-apoptotic DAPK1 in the CXCR1+ subset. The IL-2 producers were more frequently found in the IL-7R+ subset of the CXCR1- effector CD8+ T cells than in the IL-7R- subset. IL-7/IL-7R signaling promoted cell survival only in the CXCR1- subset. The present study has highlighted a novel subset of effector CD8+ T cells producing IL-2 and suggests the importance of this subset in the homeostasis of effector CD8+ T cells.
Functional heterogeneity of human effector CD8+ T cells.
Sex, Specimen part
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 SamplesTo examine the expressions of HSF1 and SSBP1-mediated gene in control and heat shock conditions, we performed DNA microarray analysis.
Mitochondrial SSBP1 protects cells from proteotoxic stresses by potentiating stress-induced HSF1 transcriptional activity.
Specimen part, Treatment
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