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GSE62923
Homo sapiens
46 Downloadable Samples
Illumina HiSeq 2000, Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 28 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20), Illumina HiSeq 2000
Description
Activation of CD4 T cells is a reaction to challenges such as microbial pathogens, cancer and toxins that defines adaptive immune responses. The roles of T cell receptor crosslinking, intracellular signaling, and transcription factor activation are well described, but the importance of post-transcriptional regulation by RNA-binding proteins (RBPs) has not been considered in depth. We describe a new model expanding and activating primary human CD4 T cells and applied this to characterizing activation-induced assembly of splicing factors centered on U2AF2. We immunoprecipitated U2AF2 to identify what mRNA transcripts were bound as a function of activation by TCR crosslinking and costimulation. In parallel, mass spectrometry revealed the proteins incorporated into the U2AF2-centered RNA/protein interactome. Molecules that retained interaction with the U2AF2 complex after RNAse treatment were designated as central interactome members (CIMs). Mass spectrometry also identified a second class of activation-induced proteins, peripheral interactome members (PIMs), that bound to the same transcripts but were not in physical association with U2AF2 or its partners. siRNA knockdown of two CIMs and two PIMs caused changes in activation marker expression, cytokine secretion, and gene expression that were unique to each protein and mapped to pathways associated with key aspects of T cell activation. While knocking down the PIM, SYNCRIP, impacts a limited but immunologically important set of U2AF2-bound transcripts, knockdown of U2AF1 significantly impairs assembly of the majority of protein and mRNA components in the activation-induced interactome. These results demonstrated that CIMs and PIMs, either directly or indirectly through RNA, assembled into activation-induced U2AF2 complexes and play roles in post-transcriptional regulation of genes related to cytokine secretion. These data suggest an additional layer of regulation mediated by the activation-induced assembly of RNA splicing interactomes that is important for understanding T cell activation.
Publication Title
The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HiSeq 2000, Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Activation of CD4 T cells is a reaction to challenges such as microbial pathogens, cancer and toxins that defines adaptive immune responses. The roles of T cell receptor crosslinking, intracellular signaling, and transcription factor activation are well described, but the importance of post-transcriptional regulation by RNA-binding proteins (RBPs) has not been considered in depth. We describe a new model expanding and activating primary human CD4 T cells and applied this to characterizing activation-induced assembly of splicing factors centered on U2AF2. We immunoprecipitated U2AF2 to identify what mRNA transcripts were bound as a function of activation by TCR crosslinking and costimulation. In parallel, mass spectrometry revealed the proteins incorporated into the U2AF2-centered RNA/protein interactome. Molecules that retained interaction with the U2AF2 complex after RNAse treatment were designated as central interactome members (CIMs). Mass spectrometry also identified a second class of activation-induced proteins, peripheral interactome members (PIMs), that bound to the same transcripts but were not in physical association with U2AF2 or its partners. siRNA knockdown of two CIMs and two PIMs caused changes in activation marker expression, cytokine secretion, and gene expression that were unique to each protein and mapped to pathways associated with key aspects of T cell activation. While knocking down the PIM, SYNCRIP, impacts a limited but immunologically important set of U2AF2-bound transcripts, knockdown of U2AF1 significantly impairs assembly of the majority of protein and mRNA components in the activation-induced interactome. These results demonstrated that CIMs and PIMs, either directly or indirectly through RNA, assembled into activation-induced U2AF2 complexes and play roles in post-transcriptional regulation of genes related to cytokine secretion. These data suggest an additional layer of regulation mediated by the activation-induced assembly of RNA splicing interactomes that is important for understanding T cell activation.
Publication Title
The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Cell-cell communication is critical for stem cell maintenance. Shoot apical meristem (SAM) located at the shoot tip harbors stem cells within the central zone (CZ). Their progeny differentiate in the adjacent peripheral zone (PZ). WUSCHEL (WUS) is a homeodomain transcription factor produced in a few cells of the organizing center (OC), located beneath the CZ. It has been shown to specify stem cell fate and also activate CLAVATA3 (CLV3) expression in cells of the CZ. CLV3 is a secreted peptide that activates a membrane bound receptor kinase-CLAVATA1 to restrict WUS transcription to the OC. It has been hypothesized that WUS activates CLV3 expression and stem cell fate in adjacent cells of the CZ by activating a non-cell autonomous signal. Contrary to this hypothesis, here we show that the WUS protein after being synthesized in cells of the OC, migrates into the superficial cell layers of the CZ where it activates CLV3 transcription by binding to its promoter elements. WUS also migrates laterally into the PZ to repress the expression of differentiation promoting transcription factors by binding to their regulatory regions. Migration of a stem cell inducing transcription factor into adjacent cells to activate a negative regulator, whereby restricting its own accumulation is unique to plant stem cell niches. While stem cell promoting transcription factor directly repressing differentiation promoting transcription factors to prevent premature differentiation of stem cell progenitors is conserved among diverse stem cell niches.
Publication Title
Plant stem cell maintenance involves direct transcriptional repression of differentiation program.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Differential gene expression assessed in siTNF-OMe-P treated animals showed significant correlation between improved colon integrity and clinical parameters of colitis with reduced TLR activation, tissue regeneration and reduced pro-inflammatory cytokines, as compared to all treatment groups.
Publication Title
Functionally enhanced siRNA targeting TNFα attenuates DSS-induced colitis and TLR-mediated immunostimulation in mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
GEP of the murine cell line BAL17 (BALB/c)
Publication Title
Mechanisms of intracerebral lymphoma growth delineated in a syngeneic mouse model of central nervous system lymphoma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st), Agilent-026652 Whole Human Genome Microarray 4x44K v2 (Probe Name version)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
In preeclampsia (PE), cytotrophoblast (CTB) invasion of the uterus and spiral arteries is often shallow. Thus, the placentas role has been a focus. We hypothesized that decidual defects are an important determinant of the placental phenotype. We isolated (human) endometrial stromal cells (hESCs) from non-pregnant donors with a prior pregnancy that was complicated by severe PE (sPE). Versus controls, they failed to decidualize as demonstrated by morphological criteria and the analysis of stage-specific antigens. These results were bolstered by showing that they were transcriptionally inert. Additionally, we used laser microdissection to isolate the decidua from tissue sections of the maternal-fetal interface. Transcriptional profiling revealed sPE-associated defects in gene expression. Also, decidual cells from sPE patients, which de-differentiated in vitro, failed to re-decidualize in culture. Immediately following isolation they released factors that inhibited CTB invasion, linking a possible cause to a known effect. These data suggested that failed decidualization is an important contributor to down regulated CTB invasion in sPE. Diagnosis of this defect prior to pregnancy would enable therapies that are designed to improve decidualization, a novel strategy for prevention.
Publication Title
Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The presence of some malignancies, such as cancer, impacts on peripheral blood mononuclear cells (PBMCs) gene expression profiling, suggesting the potential suitability of these genes as diagnostic and prognostic markers.
Publication Title
Transcriptional profiling of peripheral blood in pancreatic adenocarcinoma patients identifies diagnostic biomarkers.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Somatic mutations in calreticulin (CALR) are present in approximately 40% of patients with myeloproliferative neoplasms (MPN). However, the mechanism by which mutant CALR is oncogenic is unknown. Here, we demonstrate that a megakaryocytic-specific MPN phenotype is induced when mutant CALR is over-expressed in mice and that the thrombopoietin receptor, MPL is required for mutant CALR driven transformation. Whole transcriptome analysis reveals enrichment of STAT signatures in mutant CALR transformed cells and JAK2 inhibitor treatment abrogates STAT activation. Employing extensive mutagenesis-based structure-function analysis we demonstrate that the positively charged amino acids within the mutant CALR C-terminus are required for cellular transformation through facilitating physical interaction between mutant CALR and MPL. Together, our findings elucidate a novel mechanism of cancer pathogenesis. Overall design: Transcriptomes derived from BA/F3-MPL cells transformed with human wild-type CALR, human mutant CALR 52bp del, or Empty vector, at time zero (t0) and 24 hours (t24) after IL3-withdrawal culture were generated by deep sequencing, two replicas, by HiSeq2000.
Publication Title
Mutant Calreticulin Requires Both Its Mutant C-terminus and the Thrombopoietin Receptor for Oncogenic Transformation.
Sample Metadata Fields
Cell line, Subject
View Samples