EGR1 and the MAPKinase pathway provide a focus for signal integration in antibody secreting cells
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PROVIDER: PRJNA492889 | ENA |
REPOSITORIES: ENA
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Project description:EGR1 and the MAPKinase pathway provide a focus for signal integration in antibody secreting cells (LTC data set)
| PRJNA492891 | ENA
Project description:EGR1 and the MAPKinase pathway provide a focus for signal integration in antibody secreting cells (STC data set)
| PRJNA492892 | ENA
Project description:Antibody secreting cells (ASCs) survive in niche microenvironments as mature plasma cells, but how niche signals are integrated is poorly understood. Here we dissect such a response in human ASCs using an in vitro model, time course expression data, and a parsimonious gene correlation networking approach (PGCNA), we map expression changes that occur during the maturation to quiescent PCs. We demonstrate that TGF-beta, a niche factor, drives a focused effect on gene expression, including up-regulation of CXCR4, while progression to secretory optimization is completed. Heightened expression of CXCR4 in the presence of TGF-beta is in turn associated with enhanced ERK activation in response to SDF1. Mapping expression changes following SDF1/TGF-beta signaling we identify a module of immediate early genes including EGR1 as a primary nexus, upstream of subsequent waves of gene expression including genes encoding membrane proteins, such as solute channels and surface receptors. We conclude that niche signals delivered from SDF1 and TGFB integrate at the level of MAPkinase pathway and link downstream to changes in potential capacity for further niche sensing.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.
2019-02-13 | GSE120368 | GEO
Project description:Antibody secreting cells (ASCs) survive in niche microenvironments as mature plasma cells, but how niche signals are integrated is poorly understood. Here we dissect such a response in human ASCs using an in vitro model, time course expression data, and a parsimonious gene correlation networking approach (PGCNA), we map expression changes that occur during the maturation to quiescent PCs. We demonstrate that TGF-beta, a niche factor, drives a focused effect on gene expression, including up-regulation of CXCR4, while progression to secretory optimization is completed. Heightened expression of CXCR4 in the presence of TGF-beta is in turn associated with enhanced ERK activation in response to SDF1. Mapping expression changes following SDF1/TGF-beta signaling we identify a module of immediate early genes including EGR1 as a primary nexus, upstream of subsequent waves of gene expression including genes encoding membrane proteins, such as solute channels and surface receptors. We conclude that niche signals delivered from SDF1 and TGFB integrate at the level of MAPkinase pathway and link downstream to changes in potential capacity for further niche sensing.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.
2019-02-13 | GSE120367 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-02-13 | GSE120369 | GEO
Project description:Human bone marrow stromal cells (BMSCs) are key elements of the hematopoietic environment and they play a central role in bone and bone marrow physiology. However, how key BMSC functions are regulated is largely unknown. We analyzed the role of the immediate early response transcription factor EGR1 as key BMSC regulator and found that EGR1 was highly expressed in prospectively-isolated primary BMSCs, downregulated upon culture, and lower in non-CFU-F-containing CD45neg BM cells. Furthermore, EGR1 expression was lower in proliferative regenerating adult and fetal primary cells compared to adult steady-state BMSCs. Accordingly, EGR1 overexpression markedly decreased BMSC proliferation but considerably improved hematopoietic stroma support function as indicated by an increased production of transplantable CD34+CD90+ hematopoietic stem cells in expansion co-cultures. The improvement of BMSC stroma support function was mediated by increased expression of hematopoietic supporting genes, such as VCAM1 and CCL28. On the other hand, EGR1 knockdown increased ROS-mediated BMSC proliferation, and clearly reduced BMSC hematopoietic stroma support potential. These findings thus show that EGR1 is a key BMSC transcription factor with a dual role in regulating proliferation and hematopoietic stroma support function that is controlling a genetic program to coordinate the specific functions of BMSC in their different biological contexts.
2019-06-27 | PXD011767 | Pride
Project description:Transcriptional profiling of human peripheral B cell subsets sorted by flow cytometry based on the secretion of IL-10 in response to CpG2006 stimulation. Goal was to identify molecular markers to distinguish IL-10-producing B cells form non-IL-10-producing B cells. Two-condition experiment, non-IL-10-secreting B cells vs. IL-10-secreting B cells. Healthy donors. Biological replicates: 6
2013-03-04 | E-GEOD-35002 | biostudies-arrayexpress
Project description:To gain insight into the function of DNA-PKcs within immune cells, we performed a quantitative phosphoproteomic screen in T cells to identify first order phosphorylation targets of DNA-PKcs. Results indicate that DNA-PKcs phosphorylates the transcription factor Egr1 (early growth response protein 1) at S301. Expression of Egr1 is induced early upon T cell activation and dictates T cell response by modulating expression of cytokines and key costimulatory molecules. Mutation of serine 301 to alanine via CRISPR-Cas9 resulted in increased proteasomal degradation of Egr1 and a decrease in Egr1-dependent transcription of IL2 (interleukin-2) in activated T cells. Our findings identify DNA-PKcs as a critical intermediary link between T cell activation and T cell fate and a novel phosphosite involved in regulating Egr1 activity.
2021-12-21 | PXD026352 | Pride
Project description:A model of tumor metastasis based on v-src transformed immortalized cell lines was developed. The model consists of highly metastatic PR9692 cell line and a derived clone PR9692-E9 which has lost the metastatic abilities. Introduction of exogenous EGR1 gene into the non-metastasizing PR9692-E9 cells completely restores the metastatic potential. Revealed changes in gene expression provide insight into the molecular mechanisms contolling metastatic behavior of sarcoma cells. Comparison of expression profiles obtained from highly metastatic PR9692 cell line, derived non-metastatic clone PR9692-E9 and non-metastatic PR9692-E9 cells infected with replication-defective retroviral vector SFCVneo-EGR1 containing full length cDNA of EGR1. For each condition three biological replicates were analyzed.
2010-04-06 | E-GEOD-15141 | biostudies-arrayexpress
Project description:EGR1-mediated ibrutinib resistance
| PRJNA925145 | ENA