Rapid Mast Cell Generation from Gata2 Reporter Pluripotent Stem Cells

Mast cells are tissue-resident immune cells. Their overgrowth/overactivation results in a range of common distressing, sometimes life-threatening disorders, including asthma, psoriasis, anaphylaxis, and mastocytosis. Currently, drug discovery is hampered by use of cancer-derived mast cell lines or primary cells. Cell lines provide low numbers of mature mast cells and are not representative of in vivo mast cells. Mast cell generation from blood/bone marrow gives poor reproducibility, requiring 8–12 weeks of culture. Here we report a method for the rapid/robust production of mast cells from pluripotent stem cells (PSCs). An advantageous Gata2Venus reporter enriches mast cells and progenitors as they differentiate from PSCs. Highly proliferative mouse mast cells and progenitors emerge after 2 weeks. This method is applicable for rapid human mast cell generation, and could enable the production of sufficient numbers of physiologically relevant human mast cells from patient induced PSCs for the study of mast cell-associated disorders and drug discovery. [Display omitted] •Efficient mast cell production is achieved with novel Gata2-reporter PSCs•14-day Gata2-reporter PSC culture produces mast cells and self-renewing progenitors•Gata2-reporter mast cells have high protease content and degranulate•Gata2-reporter iPSC method advances prospects for human mast cell research In this article, Dzierzak and colleagues show the rapid and robust production of physiologically relevant mast cells from mouse ESCs via an innovative approach using a Gata2 reporter. This method is applicable to human mast cell production and provides the opportunity for research into patient-specific mast cell disorders.