This SuperSeries is composed of the SubSeries listed below.
Epigenetic Networks Regulate the Transcriptional Program in Memory and Terminally Differentiated CD8+ T Cells.
Specimen part, Treatment
View SamplesEpigenetic mechanisms play a critical role during differentiation of T cells by contributing to the formation of stable and heritable transcriptional patterns. To further study the mechanisms of memory maintenance in CD8+ T cells, we performed genome-wide analysis of DNA methylation, histone marking (H3K9Ac and H3K9me3) and gene expression profiles in naive, effector memory (EM) and terminally differentiated memory (TEMRA) cells. Our results indicate that DNA demethylation and histone acetylation are coordinated to generate the transcriptional program associated with memory cells. Conversely, EM and TEMRA cells share a very similar epigenetic landscape. Nonetheless, the TEMRA transcriptional program predicts an innate immunity phenotype associated with genes never reported in these cells, including several mediators of NK cell activation (VAV3 and LYN) and a large array of NK receptors (KIR2DL3, KIR2DL4, KIR2DL1, KIR3DL1, KIR2DS5, etc.). In addition, we identified up to 161 genes that encode transcriptional regulators, some of unknown function in CD8+ T cells, that were differentially expressed in the course of differentiation. Overall, these results provide new insights into the regulatory networks involved in memory CD8+ T cell maintenance and T cell terminal differentiation.
Epigenetic Networks Regulate the Transcriptional Program in Memory and Terminally Differentiated CD8+ T Cells.
Specimen part
View SamplesEpigenetic mechanisms play a critical role during differentiation of T cells by contributing to the formation of stable and heritable transcriptional patterns. To further study the mechanisms of memory maintenance in CD8+ T cells, we performed genome-wide analysis of DNA methylation, histone marking (H3K9Ac and H3K9me3) and gene expression profiles in naive, effector memory (EM) and terminally differentiated memory (TEMRA) cells. Our results indicate that DNA demethylation and histone acetylation are coordinated to generate the transcriptional program associated with memory cells. Conversely, EM and TEMRA cells share a very similar epigenetic landscape. Nonetheless, the TEMRA transcriptional program predicts an innate immunity phenotype associated with genes never reported in these cells, including several mediators of NK cell activation (VAV3 and LYN) and a large array of NK receptors (KIR2DL3, KIR2DL4, KIR2DL1, KIR3DL1, KIR2DS5, etc.). In addition, we identified up to 161 genes that encode transcriptional regulators, some of unknown function in CD8+ T cells, that were differentially expressed in the course of differentiation. Overall, these results provide new insights into the regulatory networks involved in memory CD8+ T cell maintenance and T cell terminal differentiation.
Epigenetic Networks Regulate the Transcriptional Program in Memory and Terminally Differentiated CD8+ T Cells.
Specimen part, Treatment
View SamplesCompares shFOXO4 vs. Control in LNCaP grown in culture, or in nude mice as primary orthotopic tumors or lymph node metastases
A genome-wide RNAi screen identifies FOXO4 as a metastasis-suppressor through counteracting PI3K/AKT signal pathway in prostate cancer.
Specimen part
View SamplesTo understand the role of LSD1 in B cell differentiation, mice with B cell conditional deletion of LSD1 were intravenously inoculated with LPS. After 3 days, B220+GL7-CD138- naïve B cells and CD138+ plasmablasts were FACS-sorted from the spleens and RNA-seq was performed to identify LSD1-target regulated genes. Overall design: RNA-seq on control or LSD1-deficient murine naïve B cells or plasmablasts.
The Histone Demethylase LSD1 Regulates B Cell Proliferation and Plasmablast Differentiation.
Sex, Specimen part, Cell line, Subject
View SamplesPneumocystis is a pathogen of immunocompromised hosts but can also infect healthy hosts, in whom infection is rapidly controlled and cleared. To better understand the immune mechanisms contributing to clearance of infection, microarray methods were used to examine differential gene expression in the lungs of C57BL/6 and CD40 ligand knock-out (CD40L-KO) mice over time following exposure to Pneumocystis. Immuncompetent C57BL/6 mice, which control and clear infection efficiently, showed a robust response to infection characterized by the upregulation of 349 primarily immune-response associated genes. Temporal changes in the expression of these genes suggested that there was an early (week 2) primarily innate response, that waned without controlling infection; this were followed by primarily adaptive immune responses that peaked at week 5 and successfully cleared the infection. In conjunction with the latter, there was an increased expression of B cell associated (immunoglobulin) genes at week 6 that persisted through 11 weeks. In contrast, CD40L-KO mice, which are highly susceptible to developing severe Pneumocystis pneumonia, showed essentially no upregulation of immune-response associated genes at days 35 to 75. Immunohistochemical staining supported these observations by demonstrating an increase in CD4+, CD68+, and CD19+ cells in C57BL/6 but not CD40L-KO mice. Thus, the healthy host demonstrates a robust biphasic response to infection by Pneumocystis; CD40 ligand is an essential upstream regulator of the adaptive immune responses that efficiently control infection and prevent development of progressive pneumonia.
Immune responses to Pneumocystis murina are robust in healthy mice but largely absent in CD40 ligand-deficient mice.
No sample metadata fields
View SamplesTo understand the role of EZH2 in Plasmablast function EZH2 was inducibly deleted using tamoxifen and B cells stimulated to differentiate with LPS in vivo. After 3 days, CD138+ cells were enriched from the spleens and RNA-seq was performed to identify the genes targeted by EZH2 for repression. Overall design: RNAseq on control or EZH2-deficient murine plasmablasts.
EZH2 Represses the B Cell Transcriptional Program and Regulates Antibody-Secreting Cell Metabolism and Antibody Production.
Sex, Specimen part, Cell line, Treatment, Subject
View SamplesAberrant forms of the SWI/SNF chromatin remodeling complex are associated with human disease. Loss of the Snf5 subunit of SWI/SNF is a driver mutation in pediatric rhabdoid cancers and forms aberrant sub-complexes that are not well characterized. We determined the effects of loss of Snf5 on the composition, nucleosome binding, recruitment and remodeling activities of yeast SWI/SNF. The Snf5 subunit interacts with the ATPase domain of Snf2 and forms a submodule consisting of Snf5, Swp82 and Taf14 as shown by mapping SWI/SNF subunit interactions by crosslinking-mass spectrometry and subunit deletion followed by immunoaffinity chromatography. Snf5 promoted binding of the Snf2 ATPase domain to nucleosomal DNA, enhanced its catalytic activity and facilitated nucleosome remodeling. Snf5 was required for acidic transcription factors to recruit SWI/SNF to chromatin. RNA-seq analysis suggested that both the recruitment and catalytic functions mediated by Snf5 are required for SWI/SNF regulation of gene expression. Overall design: Determining the effects of loss of Snf5 on the composition, nucleosome binding, recruitment, remodeling activities and gene expression profile of yeast SWI/SNF
Loss of Snf5 Induces Formation of an Aberrant SWI/SNF Complex.
Cell line, Subject
View SamplesTo identify a prognostic gene signature accounting for the distinct clinical outcomes in ovarian cancer patients
A gene signature predicting for survival in suboptimally debulked patients with ovarian cancer.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Gene Expression Profiling of Ewing Sarcoma Tumors Reveals the Prognostic Importance of Tumor-Stromal Interactions: A Report from the Children's Oncology Group.
Sex, Age, Disease
View Samples