Understanding mast cell heterogeneity at single cell resolution

Bulk proteomic and transcriptomic studies show that mouse and human mast cells are unique in the immune system. Numerous proteins, typically expressed in non-immune cells, are expressed in different tissue-resident mast cells under basal conditions or upon stimulation. Single-cell RNA-sequencing studies are uncovering the developmental and functional heterogeneity of mast cells in different mouse and human tissues, as well as disease conditions. Recent findings indicate that mast cells have a dual developmental origin in mice and humans. In mice, bone marrow-derived and yolk sac-derived mast cells populate distinct tissues and have both common and distinct transcriptional profiles. Recent studies are revealing how the chromatin landscape of human mast cells undergoes a genome-wide reorganization upon activation with different stimuli. Several chromatin-associated proteins regulate mast cell differentiation and proliferation in mice and humans. Mast cells (MC)s are evolutionarily conserved, tissue-resident immune cells with diverse roles in allergy, cancer, and protection from infection by helminths and microorganisms. The significant diversity in MC development and tissue-specific functional characteristics has recently begun to be understood. Exciting developments in single-cell-based RNA, protein, and chromatin profiling technologies offer new opportunities to characterize MC heterogeneity and to uncover novel MC functions and subtypes; these developments might lead to new and clinically effective therapies for certain pathologies. In this review, we provide an overview of the current understanding of MC development and heterogeneity and discuss new insights gained from single-cell-based studies that may lead to future research directions and therapeutic opportunities. Mast cells (MC)s are evolutionarily conserved, tissue-resident immune cells with diverse roles in allergy, cancer, and protection from infection by helminths and microorganisms. The significant diversity in MC development and tissue-specific functional characteristics has recently begun to be understood. Exciting developments in single-cell-based RNA, protein, and chromatin profiling technologies offer new opportunities to characterize MC heterogeneity and to uncover novel MC functions and subtypes; these developments might lead to new and clinically effective therapies for certain pathologies. In this review, we provide an overview of the current understanding of MC development and heterogeneity and discuss new insights gained from single-cell-based studies that may lead to future research directions and therapeutic opportunities. epidermal growth factor receptor ligand, whose expression is elevated under different inflammatory conditions. nematode parasite. chronic medical condition with asthma, sinus disease with recurrent nasal polyps, and sensitivity to aspirin and other non-steroidal anti-inflammatory drugs. This severe disease subset is accompanied by increased MC numbers and activation. chromatin profiling technique used to investigate genome-wide chromatin accessibility using a highly mutated Tn5 transposase, which binds, cleaves, and adds adaptors to open chromatin regions for DNA sequencing. genomic regions where extension of epigenetic mark H3K4me3 into gene bodies occurs. symptomatic inflammation of the nasal passages and paranasal sinuses of at least 12 weeks duration. skin disorder characterized by itchy wheals (hives), angioedema, or both, for 6 weeks or more without a specific external stimulus. method for performing scRNA-seq together with quantitative and qualitative information on surface proteins with available antibodies. DNA nucleotides generated via in vitro selection to selectively bind to a target. collection of cell bodies of neurons perceiving different sensations from the peripheral body parts. first oxidative product in the active demethylation of 5-methylcytosine (5mC), mediated by TET enzymes. histone mark associated with active chromatin regions, including gene promoters and enhancers. enzyme which catalyzes the conversion of histidine to histamine; essential granule component of MCs. tool for labeling cells with a unique lineage barcode that can be identified during scRNA-seq. emerging field; studies are used to map and quantify a complete set of lipids. induces crucial modifications of genomic regions required for the differentiation of specialized cell types. a field in which studies are used to map and quantify proteins or their post-translational modifications. condition in which two sexes of the same species differ beyond their sexual organs. Body size, shape, and color are typical examples of sexually dimorphic traits. four-carbon short-chain fatty acid, produced through microbial fermentation of dietary fibers in the lower intestinal tract. sequencing method to investigate gene expression at the single-cell level. widespread nematode parasite causing a disease called trichinosis. immune response characterized by the production of IL-4, IL-5, and IL-13; key against helminth infections. It also plays an important role in the pathophysiology of allergic diseases. uncommon form of urticaria caused by a vibratory stimulus in the skin. membranous structure located outside of the embryo where primitive hematopoiesis starts during embryonic development.