To determine the role of the cytokine activin A in the regulation of human T follicular helper (Tfh) cell gene program, we performed a transcriptomic analysis (RNA-seq) of human naïve CD4 T cells differentiated in vitro with activin A. The analysis of the gene expression profile driven by activin A, alone or in combination with IL-12 (a know regulator of human Tfh differentiation/function), revealed that activin A can regulate the expression of multiple molecules involved in the differentiation and/or function of human Tfh cells. Overall design: Human naïve CD4 T cells were isolated from fresh PBMCs of healthy control subjects by magnetic bead isolation. Purity was measured by FACS as percentage of CD4+CD45RA+ cells and was 95% or higher. Upon isolation, naïve CD4 T cells were stimulated with anti-CD3/CD28 coated beads in the presence of the following cytokine combinations: no exogenous cytokines (beads only), activin A, IL-12, activin A+IL-12, TGFb, TGFb +IL12. Following 5 days of in vitro culture, live CD4 T cells were FACS sorted and gene expression was analyzed by RNA-seq. Data are from independent donors.
Activin A programs the differentiation of human TFH cells.
No sample metadata fields
View SamplesWe describe GC-Tfr, a population of CD25 negative Foxp3 positive CXCR5hiPD1hiBCL6hi T-follicular regulatory cells that preferentially localise in the germinal centers. Male C57BL/6 Foxp3-DTR-GFP reporter mice were vaccinated with NP-Ova in Alum and 7 days later cells sorted before RNA-sequencing. Analysis revealed that GC-Tfr have a gene expression pattern equidistant between Tregs and Tfh, but fundamentally retain their suppressive characteristics as regulatory cells.
A distinct subpopulation of CD25<sup>-</sup> T-follicular regulatory cells localizes in the germinal centers.
Sex, Specimen part, Cell line
View SamplesT-follicular helper cells (Tfh) differentiate through a multistep process culminating in germinal center (GC) resident GC-Tfh that provide support to GC B-cells. T-follicular regulatory cells (Tfr) have been shown to have critical roles in the control of Tfh and germinal center formation. While Tfh cells are inhibited by IL-2, Treg cells depend on it. Here we describe a novel CD25 negative subset within both murine and human PD1+CXCR5+Foxp3+ Tfr that is preferentially located in the GC and can be clearly differentiated from non-GC Tfr, Tfh and effector Tregs by expression of a wide range of molecules. In comparison to Tfr and effector Tregs, GC-Tfr cells partially downregulate IL-2 dependent canonical Treg features, but retain suppressive function, while simultaneously upregulating genes associated with Tfh and GC-Tfh. We suggest that, similar to Tfh, Tfr follow a differentiation pathway culminating in a distinct GC resident subset, GC-Tfr.
A distinct subpopulation of CD25<sup>-</sup> T-follicular regulatory cells localizes in the germinal centers.
Sex, Age, Specimen part
View SamplesIn this study we have examined the effect of sub-cytotoxic exposure to aristolochic acids (1.65M) at 6h, 24h and 72h on the whole-genome expression profile in a rat proximal renal tubule cell line (NRK-52E).
Aristolochic acids - Induced transcriptomic responses in rat renal proximal tubule cells in vitro.
Cell line, Time
View SamplesA fundamental question in biology is how gene expression is regulated to give rise to a phenotype. However, transcriptional variability is rarely considered and could influence the relationship between genotype and phenotype. It is known in unicellular organisms that gene expression is often noisy rather than uniform and has been proposed to be beneficial when environmental conditions are unpredictable. However, little is known about transcriptional variability in multicellular organisms. Using transcriptomic approaches, we analysed gene expression variability over a 24 hours time-course between individual Arabidopsis thaliana plants growing in stable conditions. We identified hundreds of genes that exhibit high inter-individual variability and found that many are involved in environmental responses. We also identified factors that might facilitate gene expression variability, such as gene size, the number of transcription factors regulating a gene and the chromatin environment. These results will bring a new light into the impact of transcriptional variability in gene expression regulation in plants. Overall design: RNA-seq were generated for 14 individual seedlings for each of the 12 following time points: ZT2, ZT4, ZT6, ZT8, ZT10, ZT12 (just before dusk), ZT14, ZT16, ZT18, ZT20, ZT22 and ZT24 (just before dawn).
Widespread inter-individual gene expression variability in <i>Arabidopsis thaliana</i>.
Specimen part, Subject, Time
View SamplesMonocytes were induced to mature to macrophages with M-CSF. Cells were then activated with Interferon gamma and LPS or IL-4.
Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression.
No sample metadata fields
View SamplesChemotherapy may cause DNA damage within the oral mucosa of cancer patients leading to mucositis, a dose-limiting side effect for effective cancer treatment.
Microarray analyses of oral punch biopsies from acute myeloid leukemia (AML) patients treated with chemotherapy.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer.
Cell line
View Samples10 Breast cancer cell lines profiled on the Affymetrix U133 Plus 2.0 platform used in conjunction with matched DNA copy number and DNA methylation data for integrative analysis.
An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer.
Cell line
View SamplesPTEN is thought to play a critical role in T cell activation by negatively regulating the PI3K signaling pathway important for cellular activation, growth, and proliferation. T cells from mice in which PTEN was conditionally deleted in the thymus were reported to display CD28-independent IL-2 production and relative resistance to anergy induction. However, such observations could have stemmed from alterations in T cell development due to early deletion in thymocytes. To directly eliminate PTEN in post-thymic T cells, we utilized CAR Tg x PTENflox/flox mice which enabled gene deletion using a Cre adenovirus in vitro. Gene expression profiling revealed a small subset of induced genes that were augmented upon PTEN deletion and T cell stimulation. Our results indicate that deletion of PTEN can augment the activation of post-thymic T cells. Nonetheless, PTEN inhibition may be a viable target for immune potentiation due to increased cytokine production by activated CD4+ cells.
Conditional deletion of PTEN in peripheral T cells augments TCR-mediated activation but does not abrogate CD28 dependency or prevent anergy induction.
Specimen part
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