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Homo sapiens
63 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A dichotomy of gene regulatory associations during the activated B-cell to plasmablast transition.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 63 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
The activated B-cell (ABC) to plasmablast transition is the cusp of antibody secreting cell (ASC) differentiation but is incompletely defined. We apply expression time-courses, parsimonious gene correlation network analysis, and ChIP-seq to explore this in human cells. The transition initiates with input signal loss leading within hours from cell growth dominant programs to enhanced proliferation, accompanied from 24h by ER-stress response, secretory optimization and upregulation of ASC features. Clustering of genomic occupancy for ASC transcription factors (TFs) IRF4, BLIMP1 and XBP1 with CTCF and histone marks defines distinct patterns for each factor in plasmablasts. Integrating TF-associated clusters and modular gene expression identifies a dichotomy: XBP1 and IRF4 significantly link to gene modules induced in plasmablasts, but not to modules of repressed genes, while BLIMP1 links to modules of ABC genes repressed in plasmablasts but is not significantly associated with modules induced in plasmablasts. Pharmacological inhibition of the G9A (EHMT2) histone-methytransferase, a BLIMP1 co-factor that catalyzes repressive H3K9me2 marks, leaves functional ASC differentiation intact but de-represses ABC-state genes. Thus, in human plasmablasts IRF4 and XBP1 emerge as the dominant association with ASC gene expression, while BLIMP1 links to repressed modules with particular focus in repression of the B-cell activation state.
Publication Title
A dichotomy of gene regulatory associations during the activated B-cell to plasmablast transition.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The unfolded protein response (UPR) and activation of XBP1 is necessary for high secretory efficiency and functional differentiation of antibody secreting cells (ASCs). The UPR additionally includes a branch in which membrane-bound transcription factors, exemplified by ATF6, undergo intramembrane-proteolysis by the sequential action of site-1 (MBTPS1/S1P) and site-2 proteases (MBTPS2/S2P) and release of the cytoplasmic domain as an active transcription factor. Such regulation is shared with a family of CREB3-related transcription factors and sterol regulatory element-binding proteins (SREBPs). Of these, we identify that the CREB3 family member CREB3L2 is strongly induced and activated during the transition from B-cell to plasma cell state. Inhibition of site-1 protease leads to a profound reduction in plasmablast number linked to induction of autophagy. Plasmablasts generated in the presence of site-1 protease inhibitor segregated into CD38high and CD38low populations, the latter characterized by a marked reduction in the capacity to secrete IgG. Site-1 protease inhibition is accompanied by a distinctive change in gene expression associated with amino acid synthesis, steroid and fatty acid synthesis pathways. These result demonstrate that transcriptional control of metabolic programs necessary for secretory activity can be targeted via site-1 protease inhibition during ASC differentiation.
Publication Title
Site-1 protease function is essential for the generation of antibody secreting cells and reprogramming for secretory activity.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 63 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Plasma cells (PCs) as effectors of humoral immunity produce immunoglobulins to match pathogenic insult. However, emerging data suggests more diverse roles for PCs as regulators of immune and inflammatory responses via secretion of factors other than immunoglobulins. The extent to which such responses are pre-programmed in B-lineage cells or can be induced in PCs by the microenvironment is unknown. Here we dissect the impact of IFNs on the regulatory networks of human plasma cells. We show that core PC programs are unaffected, while PCs respond to IFNs with distinctive transcriptional responses. The ISG15-system emerges as a major transcriptional output induced in a sustained fashion by IFN- in PCs and linked both to intracellular conjugation and ISG15 secretion. This leads to the identification of ISG15-secreting plasmablasts/PCs in patients with active SLE. Thus ISG15-secreting PCs represent a distinct pro-inflammatory PC subset providing an immunoglobulin-independent mechanism of PC action in human autoimmunity
Publication Title
Network Analysis Identifies Proinflammatory Plasma Cell Polarization for Secretion of ISG15 in Human Autoimmunity.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 21 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Gene expression profiling of B-cells from a model differentiation series: from Nave B-cells, through a proliferative plasmablast stage to long-lived antibody secreting plasma cells.
Publication Title
In vitro generation of long-lived human plasma cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 221 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
OSCC is associated with substantial mortality and morbidity. To identify potential biomarkers for the early detection of invasive OSCC, we compared the gene expressions of OSCC, oral dysplasia, and normal
Publication Title
Gene expression profiling identifies genes predictive of oral squamous cell carcinoma.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Plac1 is an X-linked (Xq26) trophoblast gene expressed at high levels in the placenta, at low levels in the testis, but not in other normal somatic tissues. However, it is re-expressed in several malignancies, including breast, colon, lung, gastric, liver and endometrial cancers as well as in most human cancer cell lines. Plac1 contains HLA-A2-restricted epitopes capable of eliciting a cytotoxic T lymphocyte (CTL) response against human breast cancer cells, and colorectal cancer patients with a Plac1-specific CTL response demonstrate long-term survival. To explore the role of Plac1 in cancer, mouse mammary tumor E0771 cells expressing high levels of Plac1 were transduced with a lentivirus expressing a Plac1 shRNA (E0771/shPlac1).
Publication Title
Plac1 Is a Key Regulator of the Inflammatory Response and Immune Tolerance In Mammary Tumorigenesis.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
To determine the effect of iBET762+, a bromodomain BET inhibitor, on the transcription of 20861 and 20863 cells. These cells are subclones of W12 cells, derived from cervical intraepithelial neoplastic lesion. 20861 contains integrated HPV16 DNA and 20863 contains extrachromosomal HPV16 DNA. iBET762+ decreases expression of the HPV16 E6 and E7 oncogenes in both cell lines and this is expected to have dramatic effects on the cellular transcriptome
Publication Title
Tandemly Integrated HPV16 Can Form a Brd4-Dependent Super-Enhancer-Like Element That Drives Transcription of Viral Oncogenes.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Pathogen-specific polyfunctional T cell responses have been associated with favorable clinical outcomes but it is not known whether polyfunctional T cells are distinct from monofunctional cytokine producing T cells. In this study we compared the transcriptomic profile of P. falciparum reactive polyfunctional and IFNg monofunctional CD4 T cells by microarray analysis and show that polyfunctional CD4 T cells are associated with a unique transcriptomic signature.
Publication Title
Polyfunctional and IFN-<b>γ</b> monofunctional human CD4<sup>+</sup> T cell populations are molecularly distinct.
Sample Metadata Fields
No sample metadata fields
View Samples
SRP056378- Homo sapiens
- 1 Downloadable Sample
IlluminaHiSeq2000
Description
This study assessed the transcriptional profile of SiHa cells. SiHa is a cervical cancer cell line with integrated HPV16, and was used as a model to study human gene expression in the context of integrated virus. Gene expression in SiHa, calculated by Cufflinks, was scored in windows around the locations of known viral integrations in patients or cell lines to determine if there was an association between gene expression and viral integration. We found that SiHa gene expression was higher near loci of integration for HPV18 vs. HPV16, cervical tissues vs. head and neck cancers, and cervical cancers vs. in vitro integrations. This study provides insight into the factors that may influence where viruses integrate in the human genome. Overall design: Gene Expression in untreated SiHa cells.
Publication Title
Meta-Analysis of DNA Tumor-Viral Integration Site Selection Indicates a Role for Repeats, Gene Expression and Epigenetics.
Sample Metadata Fields
No sample metadata fields
View Samples