Polarization of macrophages to M1 or M2 cells is important for mounting responses against bacterial and helminth infection respectively. Jumonji domain containing 3 (JMJD3), a histone 3 K27 demethylase, has been implicated in the activation of macrophages. Here we show that JMJD3 is essential for M2 macrophage polarization to helminth infection and chitin, though JMJD3 is dispensable for M1 responses. Furthermore, Jmjd3 is critical for proper bone marrow macrophage differentiation in a demethylase activity-dependent manner. Jmjd3 deficiency affected trimethylation of H3K27 in only a limited numbers of genes. Among them, we identified Irf4 as the target transcription factor critical for controlling M2 macrophage polarization. Collectively, these results show that JMJD3-mediated H3K27 demethylation is critical for regulating M2 macrophage development leading to anti-helminth host responses.
The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Bifidobacteria can protect from enteropathogenic infection through production of acetate.
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View SamplesPulmonary dendritic cells are heterogenous cells comprise four distinct subsets including two conventional dendritic cell subsets, CD103+ and CD11bhiCD14lo cells, and two monocyte-derived dendritic cell subsets. Their functions in terms of migration and T cell activation are distinct, but genes regulating their features are to be determined.
Complement receptor C5aR1/CD88 and dipeptidyl peptidase-4/CD26 define distinct hematopoietic lineages of dendritic cells.
Sex, Specimen part
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Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation.
Specimen part, Cell line
View SamplesTo identify factors involved in tumorigenicity of glioma-initiating cells (GICs), we compared gene expression in GIC-like cells with and without sox11 expression.
Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation.
Specimen part, Cell line
View SamplesTo identify factors involved in glioma-initiating cells (GICs), we compared gene expression between GIC-like cells and non-GICs.
Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation.
Specimen part
View SamplesEndothelium in embryonic hematopoietic tissues generates hematopoietic stem/progenitor cells; however, it is unknown how its unique potential is specified. We show that transcription factor Scl/Tal1 is essential for both establishing the hematopoietic transcriptional program in hemogenic endothelium and preventing its misspecification to a cardiomyogenic fate. Scl-/- embryos activated a cardiac transcriptional program in yolk sac endothelium, leading to the emergence of CD31+Pdgfr+ cardiogenic precursors that generated spontaneously beating cardiomyocytes. Ectopic cardiogenesis was also observed in Scl-/- hearts, where the disorganized endocardium precociously differentiated into cardiomyocytes. Induction of mosaic deletion of Scl in Sclfl/flRosa26Cre-ERT2 embryos revealed a cell-intrinsic, temporal requirement for Scl to prevent cardiomyogenesis from endothelium. Scl-/- endothelium also upregulated the expression of Wnt antagonists, which promoted rapid cardiomyocyte differentiation of ectopic cardiogenic cells. These results reveal unexpected plasticity in embryonic endothelium such that loss of a single master regulator can induce ectopic cardiomyogenesis from endothelial cells.
Scl represses cardiomyogenesis in prospective hemogenic endothelium and endocardium.
Specimen part
View SamplesAnalysis of Foxp3(+)epigenetics(-) T cells, Foxp3(-)epigenetics(+) T cells, and Foxp3(+)epigenetics(+) T cells. Results indicate regulatory T cell (Treg) ontogenesis requires two independent processes, expression of the transcription factor Foxp3 and establishment of Treg epigenetic programs induced by T cell receptor (TCR) stimulation.
T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development.
Specimen part
View SamplesTo clarify inflammatory genes whose expression is suppressed at high temperatures, we performed comprehensive analysis of gene expression by using a DNA microarray. Two independent primary cultures of mouse embryo fibroblasts (MEF1 and MEF2) were treated with LPS for 4 hours, or treated with LPS for 4 hours after the pretreatment with heat shock at 42C for 1 hour, and we identified 100 genes that undergo more than a 3-fold increase with LPS treatment. Remarkably, 86 genes (86%) underwent less than a 2-fold increase after combined treatments with heat shock and LPS in MEF1 and MEF2 cells.
Heat shock transcription factor 1 inhibits expression of IL-6 through activating transcription factor 3.
Specimen part
View SamplesInteraction of hematopoietic progenitors with the thymic stromal microenvironment induces them to proliferate, adopt the T cell fate, and asymmetrically diverge into multiple T lineages. Progenitors at various developmental stages are stratified among different regions of the thymus, implying that the corresponding microenvironments differ from one another, and provide unique sets of signals to progenitors migrating between them. The nature of these differences remains undefined. Here we use novel physical and computational approaches to characterize these stromal subregions, distinguishing gene expression in microdissected tissues from that of their lymphoid constituents. Using this approach, we comprehensively map gene expression in functionally distinct stromal microenvironments, and identify clusters of genes that define each region. Quite unexpectedly, we find that the central cortex lacks distinctive features of its own, and instead appears to function by sequestering unique microenvironments found at the cortical extremities, and modulating the relative proximity of progenitors moving between them.
Spatial mapping of thymic stromal microenvironments reveals unique features influencing T lymphoid differentiation.
Specimen part
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