Gene expression profiles of immature versus mature bone marrow-derived basophils (BMBAs) elicited by either IL-3 or TSLP.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE206592 | GEO | 2023/03/21
REPOSITORIES: GEO
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Project description:Basophils are the least common granulocytes which represent less than 1% of peripheral blood leukocytes. Recent development of analytical tools for basophils enables us to understand their critical roles in allergic reactions and protection from parasitic infections. Nevertheless, the differentiation trajectory of basophils remains unclear. We have identified previously-unappreciated pre-basophil subpopulation which encompasses previously-defined basophil precursors (BaPs) in a series of experiments including scRNA-seq analysis (deposited to GSE206589). In this study, we explored gene expression profiles of pre-basophils and mature basophils activated by antigen/IgE-stimulation or IL-3-stimulation. We have revealed that IL-3 activated pre-basophils displayed distinct gene expression profiles from antigen/IgE- or IL-3-stimulated mature basophils, suggesting the unuque property of pre-basophils.
2023-03-21 | GSE222701 | GEO
Project description:Thymic stromal lymphopoietin (TSLP) is a type I cytokine that plays a central role in induction of allergic inflammatory responses. Its principal targets have been reported to be dendritic cells and / or CD4 T cells; epithelial cells are a principal source. We report here the development of a reporter mouse (TSLP-ZsG) in which a ZsGreen (ZsG)-encoding construct has been inserted by recombineering into a bacterial artificial chromosome (BAC) immediately at the translation initiating ATG of TSLP. The expression of ZsG by mice transgenic for the recombinant BAC appears to be a faithful surrogate for TSLP expression, particularly in keratinocytes and medullary thymic epithelials cells (mTECs). A comparison of gene expression in ZsG expressing and ZsG negative mTECs and cortical thymic epithelial cells, which are all ZsG negative, revealed that all three populations can be distinguished from one another. In particular ZsG (and TSLP) expressing mTECs and ZsG- mTECs are separable populations based on gene expression profiling. Little or no expression of ZsG is observed in bone marrow-derived mast cells or basophils or in CD45+ cells infiltrating TSLP/ZsG-expressing skin. Using the TSLP-ZsG reporter mouse, we show that TNFa and IL-4/IL-13 are potent inducers of TSLP expression by keratinocytes and that local activation of Th2 and Th1 cells induces keratinocyte TSLP expression. We suggest that the capacity of TSLP to both induce Th2 differentiation and to be induced by activated Th2 cells raises the possibility that TSLP may be involved in a positive feedback loop to enhance allergic inflammatory conditions.
2015-01-06 | GSE54343 | GEO
Project description:Extramedullary hematopoiesis (EMH) refers to the differentiation of hematopoietic stem cells (HSCs) into effector cells that occurs in compartments outside of the bone marrow. Previous studies linked pattern recognition receptor (PRR)-expressing HSCs, EMH and immune responses to microbial stimuli. However, the factors that regulate EMH and whether EMH operates in broader immune contexts remain unknown. Here, we demonstrate a previously unrecognized role for thymic stromal lymphopoietin (TSLP) in promoting the population expansion of progenitor cells in the periphery and identify that TSLP-elicited progenitors differentiate into effector cells including macrophages, dendritic cells and granulocytes that contribute to TH2 cytokine responses. The frequency of circulating progenitor cells was also increased in allergic patients with a gain-of-function polymorphism in TSLP, suggesting the TSLP-EMH pathway may operate in human disease. These data identify that TSLP-induced EMH contributes to the development of allergic inflammation and indicate that EMH is a conserved mechanism of innate immunity. In this study, we performed gene expression profiling to examine how the transcriptional signatures compared between TSLP-elcited GMP-like cells and naïve bone marrow-resident GMPs. Splenic TSLP-elicited GMP-like cells (CD3-, CD4-, CD5-, CD8-, CD19-, CD11b-, CD11c-, NK1.1-, FcεRI-, CD34+ c-kit+) were sort-purified from the spleen of C57BL/6 mice on day 5 post-TSLP-cDNA treatment. BM-resident GMPs (CD3-, CD4-, CD5-, CD8-, CD19-, CD11b-, CD11c-, NK1.1-, FcεRI-, Sca1- c-kit+ CD34+ CD16/32+) were sort-purified from mice that received a control-cDNA injection.
2014-03-28 | E-GEOD-52485 | biostudies-arrayexpress
Project description:In this study, we explored gene expression profiles of CD34-CLEC12Ahi pre-basophils isolated from the bone marrow as well as CD34-CLEC12Alo mature basophils from the bone marrow and CD34+ basophil progenitors. We revealed that the gene expression of mature basophils isolated from the bone marrow and spleen resembled each other whereas pre-basophils and mature basophils showed distinct gene expression profiles.
2023-03-21 | GSE206591 | GEO
Project description:Extramedullary hematopoiesis (EMH) refers to the differentiation of hematopoietic stem cells (HSCs) into effector cells that occurs in compartments outside of the bone marrow. Previous studies linked pattern recognition receptor (PRR)-expressing HSCs, EMH and immune responses to microbial stimuli. However, the factors that regulate EMH and whether EMH operates in broader immune contexts remain unknown. Here, we demonstrate a previously unrecognized role for thymic stromal lymphopoietin (TSLP) in promoting the population expansion of progenitor cells in the periphery and identify that TSLP-elicited progenitors differentiate into effector cells including macrophages, dendritic cells and granulocytes that contribute to TH2 cytokine responses. The frequency of circulating progenitor cells was also increased in allergic patients with a gain-of-function polymorphism in TSLP, suggesting the TSLP-EMH pathway may operate in human disease. These data identify that TSLP-induced EMH contributes to the development of allergic inflammation and indicate that EMH is a conserved mechanism of innate immunity. In this study, we performed gene expression profiling to examine how the transcriptional signatures compared between TSLP-elcited GMP-like cells and naïve bone marrow-resident GMPs.
2014-03-28 | GSE52485 | GEO
Project description:Human basophils regulate allergic immune responses by releasing histamine and effector cytokines such as interleukin 4 (IL-4) and IL-13. IL-3/IL-3R signaling axis plays key roles in the maturation, survival and activation of basophils. We and others have shown that IL-3-induced surface receptors e.g. ST2 and IL-17RB regulate the biology of basophils. We in this study aim to identify new basophil activation maker and regulator by transcriptomic analysis of IL-3-stimulated basophils.
2021-01-01 | GSE144096 | GEO
Project description:Basophils are important effector cells in allergic inflammation, anti-parasitic immune response and skin disorders. A number of activators including interleukin 3 (IL-3) and IgE have been identified in the regulation of human basophils expressing mediators such as histamine and leukotriene C4 (LTC4) and cytokines, including IL-4 and IL-13. Human basophils express high levels of IL-2 receptors. However, the function of the IL-2 pathway in basophils remains unknown. Here, we identify that IL-2-stimulated human basophils in vitro express a variety of inflammatory cytokines and chemokines including IL-5, IL-13, GM-CSF and CCL-17. Of note, one of the top regulated cytokines, IL-5, was for the first time identified to be expressed in human basophils and was distinctly regulated by IL-2, independently of IL-3 and IgE. Immunofluorescence analysis of skin specimens from bullous pemphigoid and eczema revealed that infiltrating basophils in skin lesions widely express IL-5 and GM-CSF. Together, our findings reveal IL-2 as a novel regulator of human basophils to express IL-5 and GM-CSF in skin disorders. This adds a new layer to support the importance of basophils in skin disorders.
2018-10-01 | GSE74375 | GEO
Project description:To investigate the mechanisms by which C/EBPa drives basophil differentiation and maintains basophil identity, we examined whether or not C/EBPa promotes basophil molecular programming and simultaneously represses mast cell molecular programming. We performed genome-wide gene expression profiling on basophils and mast cells and found that 6798 genes were shared by mast cells and basophils; 2033 genes were expressed 2-10 (log2 1-3.3)-fold higher in basophils (differentially expressed in basophils); and 413 genes were expressed greater than 10 (log2 3.3)-fold in basophils (highly expressed in basophils). On the other hand, we found 569 genes were expressed 2-10 (log2 -1 to -3.3) fold higher in mast cells and 171 genes were highly expressed in mast cells [greater than 10 fold (log2 -3.3)]. We treated purified basophils prepared from Cebpaf/f RosaYFP/creER mice and Cebpa+/+ RosaYFP/creER control mice with or without 4HT treatment for five days. Gene expression in the treated basophils was analyzed using microarray analysis. Overall, deletion of C/EBPa in basophils resulted in a reduction of mRNA expression for 248 genes and led to an increase in mRNA expression for 255 genes. The majority of the C/EBPa-regulated genes were either differentially or highly expressed in basophils or mast cells. In this study, we compared gene expression in basophils and mast cell and identified genes which specifically expressed in basophils and mast cells. By using Cebpa conditional knock out mice, we identified Cebpa regulated genes in basophils.
2013-04-01 | E-GEOD-41596 | biostudies-arrayexpress
Project description:We performed large-scale comparative microarrays of bone marrow -derived mast cells and basophils at rest, upon an adaptive-type action (IgE-crosslinking) or upon innate-type activation (IL-33-activation).
2017-03-17 | GSE96694 | GEO
Project description:Basophils are the least common granulocytes which represent less than 1% of peripheral blood leukocytes. Recent development of analytical tools for basophils has enabled us to understand their critical roles in allergic reactions and protection from parasitic infections. Nevertheless, the differentiation trajectory of basophils remain unclear. To explore differentiation trajectory of basophils, we conducted highly sensitive single cell RNA sequencing (scRNA-seq) of bone marrow-derived basophils (BMBAs) and basophils under homeostatic conditions. As a result, we identified previously-unappreciated pre-basophils which are located down-stream of bi-potential basophil and mast cell common precursors and upstream of mature basophils along the ontogeny of basophlis.
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