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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
- 36 Downloadable Samples
NextSeq 500
Description
Autophagy is a membrane-trafficking process that directs degradation of cytoplasmic material in lysosomes. The process promotes cellular fidelity, and while the core machinery of autophagy is known, the mechanisms that promote and sustain autophagy are less well defined. Here we report that the epigenetic reader BRD4 and the methyltransferase G9a repress a TFEB/TFE3/MITF-independent transcriptional program that promotes autophagy and lysosome biogenesis. We show that BRD4 knockdown induces autophagy in vitro and in vivo in response to some, but not all, situations. In the case of starvation, a signaling cascade involving AMPK and histone deacetylase SIRT1 displaces chromatin-bound BRD4, instigating autophagy gene activation and cell survival. Importantly, this program is directed independently and also reciprocally to the growth-promoting properties of BRD4 and is potently repressed by BRD4-NUT, a driver of NUT midline carcinoma. These findings therefore identify a distinct and selective mechanism of autophagy regulation. Overall design: RNA-Seq of KP-4 pancreatic adenocarcinoma cells transfected with control, BRD4 #1 or BRD4 #2 siRNA for 72hrs (n=3 independent sample preparations)
Publication Title
Bromodomain Protein BRD4 Is a Transcriptional Repressor of Autophagy and Lysosomal Function.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
FOXO1 is highly expressed in normal B cells and in most types of non-Hodgkinl lymphoma. In Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma(cHL) expression of FOXO1 is low or absent. We overexpressed constitutively active mutant of FOXO1 fused in frame with estrogen receptor ligand-binding domain (FOXO1(3A)ER), which can be activated by 4-Hydroxytamoxifen (4-OHT), in cHL cell lines KM-H2 and L428. Activation of the FOXO1 with 4-OHT resulted in inhibition of proliferation and apoptosis. Using gene-expression array we found that FOXO1 activates transcription of known and potential tumor suppressor genes: CDKN1B, PMAIP1, BCL2L11, TNFSF10, FBXO32, CBLB). Of note, FOXO1 repressed transcription of several cytokines and cytokine receptors, which are known tobe involved in pathogenesis of cHL (e.g. CCL5, CXCR5, TNFRSF8). Taken togather our data indicate important role of FOXO1 repression in pathogenesis of cHL.
Publication Title
FOXO1 repression contributes to block of plasma cell differentiation in classical Hodgkin lymphoma.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 26 Downloadable Samples
- Illumina humanRef-8 v1.0 expression beadchip
Description
Schizophrenia-associated miRNA were bidirectionally modulated in HEK-293, HeLa, and SH-SY5Y cell models. Results provide important insights into the current understanding of miRNA function in various cellular environments.
Publication Title
Alternative mRNA fates identified in microRNA-associated transcriptome analysis.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Resistance of Calu3 NSCLC cells to the cytotoxic nucleoside analog gemcitabine (2',2'-difluorodeoxycytidine) can be prevented as well as reversed by the rexinoid X receptor selective agonist bexarotene. This study was designed to investigate the changes in gene expression associated with gemcitabine resistance and its reversal by bexarotene. In addition to the parental Calu3 cells and the 10 cycles of treatment of the gemcitabine resistant Calu3 cells with vehicle or bexarotene, analogous treatment paradigms with gemcitabine alone as well as the combination of both compounds have been included as controls. (However, it has to be noted that in the combination treatment, cells that were re-sensitized by bexarotene have largely been removed from the culture before harvest due to the cytotoxic activity of gemcitabine.)
Publication Title
Bexarotene (LGD1069, Targretin), a selective retinoid X receptor agonist, prevents and reverses gemcitabine resistance in NSCLC cells by modulating gene amplification.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE29815- Drosophila melanogaster
- 22 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Gene expression analysis of yw follicles at S9/10a, S10B, S12, and S14; Gene expression analysis of pxt mutant follicles (f01000 and EY03052) at S10B, S12, S14
Publication Title
Drosophila eggshell production: identification of new genes and coordination by Pxt.
Sample Metadata Fields
Sex, Specimen part
View Samples