Expression data from human mast cell progenitors and mature basophils
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE69030 | GEO | 2015/12/01
SECONDARY ACCESSION(S): PRJNA284340
REPOSITORIES: GEO
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Project description:Background: Chronic spontaneous urticaria (CSU) is a common, debilitating skin disorder characterised by recurring episodes of raised, itchy and sometimes painful wheals lasting longer than 6 weeks. CSU is mediated by mast cells which are absent from peripheral blood. However, lineage-CD34hiCD117int/hiFcεRI+ cells in blood have previously been shown to represent a mast cell precursor. Methods: We enumerated FcεRI-, FcεRI+ and FcεRIhi lineage-CD34+CD117+ cells using flow cytometry in blood of patients with CSU (n=55), including 12 patients receiving omalizumab and 43 not receiving omalizumab (n=43). Twenty-two control samples were studied. Disease control and patient response to omalizumab was evaluated using the Urticaria Control Test. We performed single cell RNA sequencing (scRNA-seq) on lineage-CD34hiCD117hi blood cells from a subset of patients with CSU (n=8) and healthy controls (n=4). Results: CSU patients had more Lineage-CD34+CD117+FcεRI+ blood cells than controls. Lineage-CD34+CD117+FcεRI+ cells were significantly higher in patients with CSU who had an objective clinical response to omalizumab when compared to patients who had poor disease control 90 days after initiation of omalizumab. scRNA-seq revealed that lineage-CD34+CD117+FcεRI+ cells contained both lymphoid and myeloid progenitor lineages, with omalizumab responsive patients having proportionally more myeloid progenitors. The myeloid progenitor lineage contained small numbers of true mast cell precursors along with more immature FcεRI- and FcεRI+ myeloid progenitors. Conclusion: Increased blood CD34+CD117+FcεRI+ cells may reflect enhanced bone marrow egress in the setting of CSU. High expression of these cells strongly predicts better clinical responses to the anti-IgE therapy, omalizumab.
2024-04-30 | GSE261424 | 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: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: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:Activation of mast cells through FcεRI can result in allergic responses. The identity of mast cells progenitors is controversial, in particular whether these cells express FcεRI. Here, we performed single-cell RNA sequencing of human peripheral blood progenitors to study the appearance of FcεRI during hematopoietic progenitor differentiation.
2022-05-03 | GSE184351 | 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.
2013-04-01 | GSE41596 | GEO
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 | GSE96695 | GEO
Project description:Mast cells and basophils are developmentally related cells whose activation is a hallmark of allergy. Functionally, mast cells and basophils overlap in their ability to produce several mediators, including histamine and granule proteases, but studies have increasingly demonstrated non-redundant roles. To characterize the transcriptional heterogeneity of mast cells and basophils upon their activation, we performed large-scale comparative microarrays of murine bone marrow–derived mast cells (BMMCs) and basophils (BMBs) at rest, upon an adaptive-type activation (IgE crosslinking), or upon an innate-type activation (IL-33 stimulation). Hierarchical clustering demonstrated that BMMCs and BMBs shared specific activation-associated transcriptional signatures but differed in others, both between cell type and between activation mode. In BMMCs, IgE crosslinking upregulated 785 genes including Egr2, Ccl1, and Fxyd6, while IL-33 stimulation induced 823 genes including Ccl1, Egr2, and Il1b. Focused bioinformatics pathway analysis demonstrated that IgE activation aligned with processes such as oxidative phosphorylation, angiogenesis, and the p53 pathway. The IL-33–activated transcriptome was enriched in genes commonly altered by NF-B in response to TNF, by IL-6 via STAT3, and in response to IFN. Furthermore, BMBs activated via IgE crosslinking selectively induced immune response genes Ccl1, Il3, and Il2 compared to IL-33–stimulated BMBs. Principal-component analysis revealed key cell- and activation-specific clustering. Overall, our data demonstrate that mast cells and basophils have cell- and activation-specific transcriptional responses and suggest that context-specific gene networks and pathways may shape how the immune system responds to allergens and innate cytokines.
2017-03-17 | GSE96696 | GEO
Project description:Mast cells originate from the bone marrow and develop into c-kit+ FcεRI+ cells. As both mast cell progenitors and mature mast cells express these cell surface markers, ways validated to distinguish between the two maturation forms with flow cytometry have been lacking. We identified and sorted two distinct populations of mast cells from mouse peritoneum. Gene expression microarray analyses were used to confirm the maturation statuses of the mast cell populations.
2015-03-07 | GSE63507 | GEO
Project description:E-cadherin is a calcium-dependent cell-cell adhesion molecule extensively studied for its involvement in tissue formation, epithelial cell behavior and suppression of cancer; however its expression in the hematopoietic system hasn't received much attention. Combining single-cell RNA sequencing analyses and immunophenotyping, we revealed expression of E-cadherin in the basophil and mast cell lineages. No defect in basophil and mast cell differentiation was observed in mice lacking E-cadherin in the hematopoietic system, supporting that E-cadherin is not required per se for basophil and mast cell differentiation. Yet, we evidenced that granulocyte-monocyte progenitors expressing high levels of E-cadherin have an enriched capacity to differentiate into basophils and mast cells. Importantly, E-cadherin expression is observed on committed progenitors prior to the expression of other reported markers of these lineages. We named those progenitors pro-BMPs (pro- basophil and mast cells progenitors). Using RNA-sequencing, we demonstrated the transcriptional priming of pro-BMPs to the basophil and mast cell lineages.
2021-01-01 | GSE132122 | GEO