A5085510498- Mast cells and histamine
- Asthma and respiratory diseases
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Food Allergy and Anaphylaxis Research
- Single-cell and spatial transcriptomics
- Eosinophilic Disorders and Syndromes
- IL-33, ST2, and ILC Pathways
- melanin and skin pigmentation
- Monoclonal and Polyclonal Antibodies Research
- Click Chemistry and Applications
- Eosinophilic Esophagitis
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Polyamine Metabolism and Applications
- Acute Myeloid Leukemia Research
- Chemokine receptors and signaling
- Chronic Lymphocytic Leukemia Research
- Neonatal Respiratory Health Research
- Chronic Myeloid Leukemia Treatments
- Cell Image Analysis Techniques
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cephalopods and Marine Biology
- Veterinary Pharmacology and Anesthesia
- Advanced Fluorescence Microscopy Techniques
Karolinska University Hospital
2016-2024
Karolinska Institutet
2016-2024
Svenska Örtmedicinska Institute
2022-2024
Uppsala University
2011-2022
Medical Research Council
2017-2020
Wellcome/MRC Cambridge Stem Cell Institute
2017-2020
University of Cambridge
2017-2020
Stem Cell Institute
2019
Single-cell RNA-seq quantifies biological heterogeneity across both discrete cell types and continuous transitions. Partition-based graph abstraction (PAGA) provides an interpretable graph-like map of the arising data manifold, based on estimating connectivity manifold partitions ( https://github.com/theislab/paga ). PAGA maps preserve global topology data, allow analyzing at different resolutions, result in much higher computational efficiency typical exploratory analysis workflow. We...
Abstract Background Basophils and mast cells contribute to the development of allergic reactions. Whereas these mature effector are extensively studied, differentiation trajectories from hematopoietic progenitors basophils largely uncharted at single‐cell level. Methods We performed multicolor flow cytometry, high‐coverage RNA sequencing analyses, cell fate assays chart basophil resolution in mouse. Results Analysis cytometry data reconstructed a detailed map differentiation, including...
Mast cell accumulation is a hallmark of number diseases, including allergic asthma and systemic mastocytosis. Immunoglobulin E-mediated crosslinking the FcεRI receptors causes mast activation contributes to disease pathogenesis. The lineage one least studied among hematopoietic lineages, controversies remain about whether expression appears during progenitor stage or terminal maturation. Here, we used single-cell transcriptomics analysis reveal temporal association between appearance gene...
IgE antibodies, administered to mice together with their specific antigen, enhance antibody and CD4+ T cell responses this antigen. The effect is dependent on the low affinity receptor for IgE, CD23, must be expressed B cells. In vitro, IgE-antigen complexes are endocytosed via CD23 cells, which subsequently present antigen This mechanism has been suggested explain also IgE-mediated enhancement of immune in vivo. We recently found that CD23+ cells capture peripheral blood rapidly transport...
Abstract Single-cell RNA-seq quantifies biological heterogeneity across both discrete cell types and continuous transitions. Partition-based graph abstraction (PAGA) provides an interpretable graph-like map of the arising data manifold, based on estimating connectivity manifold partitions ( https://github.com/theislab/paga ). PAGA maps provide latent coordinates for disconnected structure in data, preserve global topology allow analyzing at different resolutions result much higher...
Mast cells originate from the bone marrow and develop into c-kit(+) FcɛRI(+) cells. Both mast cell progenitors (MCp) mature express these surface markers, ways validated to distinguish between two maturation forms with flow cytometry have been lacking. Here, we show that primary peritoneal MCp naïve mice expressed high levels of integrin β7 had a low side scatter (SSC) light profile; whereas lower SSC profile. The statuses were confirmed using three main strategies: (1) MCp, but not cells,...
Mast cells (MCs) are powerful immune that mature in the peripheral tissues from bone marrow (BM)-derived mast cell progenitors (MCp). Accumulation of MCs lung compartments where they normally absent is thought to enhance symptoms asthma. The enrichment also observed mice subjected models allergic airway inflammation. However, whether other types inflammation trigger increased number MCp, which give rise MCs, unknown. Here, mouse-adapted H1N1 influenza A was used as a model respiratory virus...
Background Immunohistochemical analysis of granule-associated proteases has revealed that human lung mast cells constitute a heterogeneous population cells, with distinct subpopulations identified. However, systematic and comprehensive cell-surface markers to study cell heterogeneity yet be performed. Methods Human were obtained from lobectomies, the expression 332 was analyzed using flow cytometry LEGENDScreen™ kit. Markers exhibited high variance selected for additional analyses reveal...
Mast cell progenitors (MCp) leave the bone marrow and migrate to peripheral tissues where they mature. Although existence of committed MCp in adult mouse human blood has been postulated, have never found. We isolated a rare population cells blood, mast lineage. These were identified as lineage- c-kit(hi) ST2+ integrin β7(hi) CD16/32(hi) cells. Moreover, major difference maturity these based on FcεRI expression was observed between Th2-prone BALB/c strain Th1-prone C57BL/6 (66% vs. 25%...
Background: Mast cells are tissue-resident inflammatory defined by their high granularity and surface expression of the high-affinity IgE receptor, FcεRI, CD117/KIT, receptor for stem cell factor (SCF). There is a considerable heterogeneity among mast cells, both phenotypically functionally. Human generally divided into two main subtypes based on protease content; mucosa-associated MCT (tryptase positive chymase negative cell) connective tissue associated-residing MCTC cell). lung exhibit in...
BackgroundSystemic mastocytosis (SM) is a haematological disease characterised by organ infiltration neoplastic mast cells. Almost all SM patients have mutation in the gene encoding tyrosine kinase receptor KIT causing D816V substitution and autoactivation of receptor. Mast cells CD34+ haematopoietic progenitors can carry mutation; however, which progenitor cell subset arises unknown. We aimed to investigate distribution single stem cells.MethodsFluorescence-activated single-cell index...
Background: Basophils are implicated in various diseases including allergies, but a comprehensive characterization of human basophils has yet to be performed at the single-cell level. Objective: We aimed generate omics-based resource circulating basophils, made accessible research community. also sought investigate basophil heterogeneity transcriptional and surface epitope levels. Methods: Circulating were analyzed using short- long-read RNA-sequencing combination with large-scale...
Studies using mouse models have revealed that mast cell progenitors are recruited from the blood circulation to lung during acute allergic airway inflammation. The discovery of a corresponding human progenitor population in has enabled study relation circulating clinical settings.To explore possible association between frequency and asthma, we assessed this recently identified with asthma outcomes inflammatory mediators asthmatic patients controls.Blood samples were obtained, spirometry was...
Abstract Patients with allergic asthma have more lung mast cells, which likely worsens the symptoms. In experimental asthma, CD11c+ cells to be present during challenge phase for several features of inflammation occur. Whether play a role Ag-induced increases is unknown. this study, we used diphtheria toxin treatment sensitized CD11c-diphtheria receptor transgenic mice deplete cells. We demonstrate that recruitment cell progenitors substantially reduced when are depleted phase. This...
Abstract Allergic asthma is a complex disease with strong genetic component where mast cells play major role by the release of proinflammatory mediators. In mouse, cell protease-6 (mMCP-6) closely resembles human version tryptase, β-tryptase. The gene that encodes mMCP-6, Tpsb2, resides close H-2 (MHC gene) on chromosome 17. Thus, when original mMCP-6 knockout mice were backcrossed to BALB/c strain, these carrying 129/Sv haplotype MHC (mMCP-6−/−/H-2bc). Further backcrossing yielded mMCP-6−/−...
Abstract IgE, forming an immune complex with small proteins, can enhance the specific antibody and CD4 + T cell responses in vivo . The effects require presence of CD23 (Fcε-receptor II) B cells, which capture IgE-complexed antigens (Ag) circulation transport them to splenic follicles. In addition, also CD11c do not express CD23, are required for IgE-mediated enhancement responses. This suggests that some type dendritic obtains IgE-Ag complexes from cells presents antigenic peptides cells....