Rapid mast cell generation from Gata2 reporter pluripotent stem cells

Mast cells are tissue-resident immune cells. Their over-growth/-activation results in a range of common distressing, sometimes life-threatening disorders, including asthma, psoriasis, anaphylaxsis 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 novel method for the rapid/robust production of mast cells from pluripotent stem cells (PSC). 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 iPSCs for the study of mast cell-associated disorders and drug discovery.