Germinal Center B-Cell gene expression comparison between Wiskott–Aldrich syndrome protein KO mice and WT mice
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ABSTRACT:
PROVIDER: PRJEB42708 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR5195750.fastq.gz | Fastqsanger.gz | |||
| ERR5195751.fastq.gz | Fastqsanger.gz | |||
| ERR5195752.fastq.gz | Fastqsanger.gz | |||
| ERR5195753.fastq.gz | Fastqsanger.gz | |||
| ERR5195754.fastq.gz | Fastqsanger.gz |
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Project description:This experiment intended to define differential gene expression between germinal center B cells expressing or not the Wiskott-Aldrich syndrome protein in mice. Sequencing was obtained on an Illumina HiSeq2500 system from Dark Zone GCB (DAPI-CD19+ GL7+IgD-CXCR4highCD86low) purified from CTL and GCBcWKO mice (n=4).
2021-06-01 | E-MTAB-10056 | biostudies-arrayexpress
Project description:gene panel of patient with Wiskott-Aldrich syndrome
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Project description:Wiskott-Aldrich syndrome (WAS) is a disorder characterized by rare X-linked genetic immune deficiency with mutations in the was gene, a gene expressed specifically in hematopoietic cells, and the spleen plays a major role in hematopoiesis and the clearance of red blood cell. However, till now, comprehensive analyses of the spleen between wild type (WT) and WASp-deficient (WAS-KO) mice, especially at the transcriptomic level, have not been studied. Here, single-cell RNA sequencing (scRNA-seq) was adopted to identify various types of immune cells and investigate the mechanism of immune deficiency. We identified 30 clusters and 10 major cell subtypes among 11, 269 cells, including B cell, T cell, dendritic cell (DC), Natural Killer (NK) cell, monocyte, macrophage, granulocyte, stem cell and erythrocyte. Meanwhile, we evaluated the gene expression differences of cell subtypes, and analyzed the differential gene expression (DEGs) and enrichment analyses to reveal the reasons for the dysfunction of these different cell populations in WAS. Furthermore, some key genes were screened out by comparing the DEGs of each cell type during specific and non-specific immunization, and further analysis showed that these key genes were newly discovered pathologically related genes in WAS-KO mice. In summary, we present a detailed single cell resolution landscape of immune cells in spleen of WAS-KO mice. These unprecedented data uncovered the transcriptional characteristics of specific and non-specific immune cells, and the key genes were identified to lay a foundation for future studies of WAS, especially in discovering novel and underexplored mechanisms to improve gene therapies for WAS.
2023-02-05 | GSE224259 | GEO
Project description:Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infections, and increased incidence of autoimmune disorders and malignancies. WAS is caused by mutations in the was gene, which is expressed exclusively in hematopoietic cells, and the spleen plays an important role in hematopoiesis and red blood cell clearance. However, to date, detailed comparative analyses of the spleen between WASp-deficient (WAS-KO) mice and WT mice, particularly at the transcriptomic level, have not been reported. Here, we investigated the differences in the transcriptomes of spleen tissues of 10-week-old WAS-KO mice. Comparison of the gene expression profiles of WAS-KO and WT mice revealed 1964 differentially expressed genes (DEGs). Among these genes, 996 DEGs were upregulated, and 968 were downregulated in WAS-KO mice. To determine the functions of the DEGs, GO and KEGG enrichment analyses were performed for significantly upregulated and downregulated DEGs, respectively. The results showed that the levels of cell senescence and apoptosis-related genes were increased, that the antigen processing and presentation mechanisms involved in the immune response were damaged, and that signal transduction processes were impaired in the spleens of WAS-KO mice. Thus, was gene deletion may lead to anemia and hemolysis-related disease, mainly due to increased osmotic fragility of red blood cells, low hemoglobin, increased bilirubin levels and increased serum ferritin. These results indicate that senescence and apoptosis of blood cells also play an important role in the occurrence of WAS. However, most studies have focused only on the immune response. Therefore, the interesting findings of this paper can provide a stronger theoretical basis for further study and help improve the treatment of WAS. We performed gene expression profiling analysis using data obtained from RNA-seq of 2 different group of WT and WAS-KO mice.
2022-10-11 | GSE214745 | GEO
Project description:Wiskott-Aldrich Syndrome-causative mutations disrupt alternative splicing and promote gene networks predisposed to hematologic malignancies
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Project description:Transcriptomic insights into the role of the spleen in a mouse model of Wiskott-Aldrich Syndrome
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Project description:A single-cell atlas of immunocyte in spleen of a mouse model of Wiskott-Aldrich Syndrome
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Project description:Productive B cell responses are critical to protect a host from infection. The spleen and lymph nodes are populated by resting follicular B cells, which can enter germinal centers upon antigen encounter. Once in the germinal center, B cells migrate between the dark and light zones, where they undergo somatic hypermutation and selection, respectively. While germinal center B cells have been studied, an intense molecular understanding of these cells/subsets (and the differences between them) is lacking.
2020-04-06 | PXD015524 | Pride
Project description:Wiskott-Aldrich syndrome (WAS) is characterized by X-linked thrombocytopenia, eczema, immunodeficiency, recurrent infections and increased risk of autoimmunity and malignancies. WAS is caused by mutations in the WAS gene, which encodes the exclusively hematopoietic WAS protein (WASp) that is classically characterized as aν actin nucleator. However, disruption of F-actin polymerization by WAS mutations can not account for many aspects of WAS pathogenesis. Ignorance of other functions of WASP precludes in-depth understanding of the pathogenic effects of mutant WASP, and therefore hampers development of effective therapy. Here we generated induced pluripotent stem cells (iPSCs) from WAS patients (WAS-iPSC) bearing different mutations and corresponding isogenic iPSCs in which the pathogenic mutations had been corrected by targeted genome editing. Hematopoietic cells differentiated from WAS-iPSCs not only recapitulated known disease phenotypes, but also revealed novel defects of WASP deficient cells. WASP co-localized with nuclear pores, nucleoli, nuclear speckles and PML bodies by immunocytochemistry and/or serial block face scanning microscopy (SBF-SEM). MudPIT (multi-dimensional protein identification technology) analysis revealed that WASP physically interacted with nuclear body components, nuclear structural proteins, chromatin modifying complexes, and many RNA-binding proteins including major components of the spliceosome. Next-generation sequencing captured a dramatic global change of alternative splicing in WAS patient cells. WAS mutation impacted splicing of multiple genes frequently mutated in myelodysplastic syndrome and other cancers. RNA sequencing showed that WAS-iPSC derived immune cells misregulated many cell cycle regulators, tumor suppressors, immune function genes and splicing factors, and activated gene networks that drive cancer development and inflammatory diseases. Together these data uncovered previously unappreciated functions of the WASP and provided a mechanistic understanding of the pathogenesis of malignancy and autoimmunity in the most severe form of WAS. These new knowledge could help develop targeted therapy for WAS in the future.
2016-03-31 | GSE77253 | GEO
Project description:Wiskott-Aldrich syndrome (WAS) is characterized by X-linked thrombocytopenia, eczema, immunodeficiency, recurrent infections and increased risk of autoimmunity and malignancies. WAS is caused by mutations in the WAS gene, which encodes the exclusively hematopoietic WAS protein (WASp) that is classically characterized as aν actin nucleator. However, disruption of F-actin polymerization by WAS mutations can not account for many aspects of WAS pathogenesis. Ignorance of other functions of WASP precludes in-depth understanding of the pathogenic effects of mutant WASP, and therefore hampers development of effective therapy. Here we generated induced pluripotent stem cells (iPSCs) from WAS patients (WAS-iPSC) bearing different mutations and corresponding isogenic iPSCs in which the pathogenic mutations had been corrected by targeted genome editing. Hematopoietic cells differentiated from WAS-iPSCs not only recapitulated known disease phenotypes, but also revealed novel defects of WASP deficient cells. WASP co-localized with nuclear pores, nucleoli, nuclear speckles and PML bodies by immunocytochemistry and/or serial block face scanning microscopy (SBF-SEM). MudPIT (multi-dimensional protein identification technology) analysis revealed that WASP physically interacted with nuclear body components, nuclear structural proteins, chromatin modifying complexes, and many RNA-binding proteins including major components of the spliceosome. Next-generation sequencing captured a dramatic global change of alternative splicing in WAS patient cells. WAS mutation impacted splicing of multiple genes frequently mutated in myelodysplastic syndrome and other cancers. RNA sequencing showed that WAS-iPSC derived immune cells misregulated many cell cycle regulators, tumor suppressors, immune function genes and splicing factors, and activated gene networks that drive cancer development and inflammatory diseases. Together these data uncovered previously unappreciated functions of the WASP and provided a mechanistic understanding of the pathogenesis of malignancy and autoimmunity in the most severe form of WAS. These new knowledge could help develop targeted therapy for WAS in the future.
2019-01-01 | GSE77129 | GEO