Signal-Transducing Adaptor Protein-2 Governs Recovery of B Lineage Lymphocytes during hematopoietic stress.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA525841 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8690200.fastq.gz | Fastqsanger.gz | |||
| SRR8690201.fastq.gz | Fastqsanger.gz | |||
| SRR8690202.fastq.gz | Fastqsanger.gz | |||
| SRR8690203.fastq.gz | Fastqsanger.gz | |||
| SRR8690204.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Signal-transducing adaptor protein-2 (STAP-2) was discovered as a c-fms/M-CSFR interacting protein and subsequently found to function as an adaptor of signaling or transcription factors. These include STAT5, MyD88 and IB kinase (IKK) in macrophages, mast cells and T cells. There is additional information about roles in several types of malignant diseases including chronic myeloid leukemia, but none concerning B lineage lymphocytes. We have now exploited gene targeted and transgenic mice to address this issue and learned that it is not required under normal, steady-state conditions. However, recovery of B cells following transplantation was augmented in the absence of STAP-2. This appeared to be restricted to cells of this lineage and myeloid rebound was unremarkable. Furthermore, all hematological parameters were normal once recovery from transplantation was complete. Overexpression of STAP-2 specifically in lymphoid cells resulted in reduced numbers of late-stage B progenitors within bone marrow. While numbers of mature peripheral B and T cells were unaffected, recovery from sub-lethal irradiation or transplantation was dramatically reduced. LPS normally suppresses B precursor expansion in response to interleukin 7, but STAP-2 deficiency made them more resistant. Preliminary RNA-Seq analyses indicate many signaling pathways in B progenitors are STAP-2 dependent. These findings suggest STAP-2 modulates formation of B lymphocytes in demand conditions. Further study of this adapter protein could suggest ways to speed recovery of humoral immunity following chemotherapy or transplantation.
2020-01-26 | GSE127939 | GEO
Project description:Signal recovery in single cell batch integration
| PRJNA1180965 | ENA
Project description:Signal-transducing adaptor protein-2 (STAP-2) was discovered as a C-FMS/M-CSFR interacting protein and subsequently found to function as an adaptor of signaling or transcription factors. These include STAT5, MyD88 and I?B kinase in macrophages, mast cells, and T cells. There is additional information about roles for STAP-2 in several types of malignant diseases including chronic myeloid leukemia, however, none have been reported concerning B lineage lymphocytes. We have now exploited gene targeted and transgenic mice to address this lack of knowledge, and demonstrated that STAP-2 is not required under normal, steady-state conditions. However, recovery of B cells following transplantation was augmented in the absence of STAP-2. This appeared to be restricted to cells of B cell lineage with myeloid rebound noted as unremarkable. Furthermore, all hematological parameters were observed to be normal once recovery from transplantation was complete. Furthermore, overexpression of STAP-2, specifically in lymphoid cells, resulted in reduced numbers of late-stage B cell progenitors within the bone marrow. While numbers of mature peripheral B and T cells were unaffected, recovery from sub-lethal irradiation or transplantation was dramatically reduced. Lipopolysaccharide (LPS) normally suppresses B precursor expansion in response to interleukin 7, however, STAP-2 deficiency made these cells more resistant. Preliminary RNA-Seq analyses indicated multiple signaling pathways in B progenitors as STAP-2-dependent. These findings suggest that STAP-2 modulates formation of B lymphocytes in demand conditions. Further study of this adapter protein could reveal ways to speed recovery of humoral immunity following chemotherapy or transplantation.
| S-EPMC7849758 | biostudies-literature
Project description:Lymphocyte activation and effector state differentiation critically depend on integration of multiple signals, including those from antigen, co-stimulatory ligand and cytokine receptors. Thus, discovery of molecular components and mechanisms underlying signal integration is vital for the understanding and control of adaptive immune responses. Stimulation of antigen receptors in lymphocytes leads to the activation of NFAT family transcription factors (TFs) as well as the inducible expression of the immune-selective IRFs, IRF4 and IRF8; the latter are differentially controlled by co-stimulatory ligand and cytokine receptor signaling. Despite their major overlapping functions in lymphocyte activation and differentiation, it has remained enigmatic if NFATs can perform signal integration with IRF4 and IRF8, via their cooperative assembly on composite genomic regulatory elements. Composite elements (CEs) provide a powerful means of signal integration by inducible TFs and despite their clear importance, CEs arguably remain the least explored elements within cis-regulomes. To test the above hypothesis, we deployed a generalizable computational strategy, which revealed a stereospecific NFAT-IRF composite element (NICE) motif that was enriched within active chromatin regions (H3K27Ac) of activated B and T lymphocytes. NICE containing DNA sequences promoted cooperative binding of NFATs with IRF4 or IRF8. Genomic analyses in activated B cells revealed co-dependent genes that undergo activation or repression and contain NICE motifs in their regulatory regions. Notably, NFATc2 and IRF8 form a positive feedforward loop and coordinately repress the Prdm1 gene by binding a NICE motif in a phylogenetically conserved region, thereby inhibiting extrafollicular plasma cell differentiation and promoting the germinal center fate of activated B cells. The NICE motif is also enriched in DNA sequences located in accessible chromatin of human lymphocytes, suggesting evolutionary conservation of its function. The cooperative assembly of NFAT family members with IRF4 and IRF8 on NICE motifs reveals a new genomic control mechanism that enables signal integration during lymphocyte activation and differentiation.
2018-10-06 | GSE104921 | GEO
Project description:Pancreatic cancer is the fourth most lethal malignancy, which is characterized by poor immunogenicity. Pancreatic cancer cells take various strategies to suppress host immune response, evade immune defenses, and facilitate tumor growth and development. As a mode of long-range intercellular communication, cancer-derived exosomes contribute to the impairment of the immune system. However, the mechanisms that induce changes in the activities of signal transduction pathways in immune cells, which are influenced by tumor-derived exosomes, are poorly understood. We treated peripheral T lymphocytes with pancreatic cancer-derived exosomes, performed RNA-seq and Gene Set Enrichment Analysis to explore the pivotal signaling pathway that mediates apoptosis in exosomes-treated T lymphocytes.
2018-06-18 | GSE115831 | GEO
Project description:Signal integration in lymphocytes via convergent genomic actions of NFATs with IRF4 and IRF8
| PRJNA414167 | ENA
Project description:Data integration to align cells across batches has become a cornerstone of single cell data analysis, critically affecting downstream results. Yet, how much biological signal is erased during integration? Currently, there are no guidelines for when the biological differences between samples are separable from batch effects, and thus, data integration involves a lot of guesswork: Cells across batches should be aligned to be “appropriately” mixed, while preserving “main cell type clusters”. We show evidence that current paradigms for single cell data integration are unnecessarily aggressive, removing biologically meaningful variation and introducing distortion. To remedy this, we present a novel statistical model and computationally scalable algorithm, CellANOVA, that harnesses experimental design to explicitly recover biological signals that are erased during single cell data integration. CellANOVA utilizes a “pool-of-controls” design concept, applicable across diverse settings, to separate unwanted variation from biological variation of interest. When applied with existing integration methods, CellANOVA allows the recovery of subtle biological signals and corrects, to a large extent, the data distortion introduced by integration. Further, CellANOVA explicitly estimates cell- and gene-specific batch effect terms which can be used to identify the cell types and pathways exhibiting the largest batch variations, providing clarity as to which biological signals can be recovered. These concepts are illustrated on studies of diverse designs, where the biological signals that are recovered by CellANOVA are validated by orthogonal assays. In particular, we show that CellANOVA is effective in the challenging case of single-cell and single-nuclei data integration, where it recovered subtle biological signals are can be validated and replicated by external data.
2024-11-08 | GSE280883 | GEO
Project description:B-cell adaptor protein (BCAP) is a multimodular, multi-functional signal transducer that regulates signal transduction processes in leukocytes including macrophages, B-cells and T-cells. In particular BCAP acts as a negative regulator of inflammatory signaling by the Toll-like receptors. Here we characterize the complex phosphorylation patterns of BCAP and use a novel protein complex trapping strategy (virotrap) to identify interaction partners. This analysis identifies known interactions with BCAP with PI3K p85 subunit and Nck, together with novel SH2 and SH3 domain adaptor proteins notably Grb2 and CRKL. We show that the SH3 domain of Grb2 can bind to BCAP independently of phosphorylation, suggesting that the SH2 domains mediate interaction with activated receptor tyrosine kinase complexes including the CD19 subunit of the B-cell receptor. Our data also suggest that PI3K p85 subunit binds to the BCAP via SH3 domains forming an inactive complex that is activated subsequently by sequential binding with the SH2 domains. Taken together our results indicate that BCAP is a complex hub that processes signals from multiple pathways in diverse immune system cells.
2019-09-16 | PXD014410 | Pride
Project description:IP of candidate adaptor Ada5/Gdi1, tagged with HA, versus Mock (untagged) replicates. IP associated RNA was assayed. A replicate experimental design type is where a series of replicates are performed to evaluate reproducibility or as a pilot study to determine the appropriate number of replicates for a subsequent experiments. GeneticModification: HA-tagged candidate gene or control replicate_design
2012-11-15 | E-GEOD-33747 | biostudies-arrayexpress
Project description:IP of candidate adaptor Ada5/Gdi1, tagged with HA, versus Mock (untagged) replicates. IP associated RNA was assayed. A replicate experimental design type is where a series of replicates are performed to evaluate reproducibility or as a pilot study to determine the appropriate number of replicates for a subsequent experiments. GeneticModification: HA-tagged candidate gene or control
2012-11-15 | GSE33747 | GEO