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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.

Original publication

DOI

10.1016/j.stemcr.2018.08.007

Type

Journal article

Journal

Stem Cell Reports

Publication Date

09/10/2018

Volume

11

Pages

1009 - 1020

Keywords

ESC, Gata2, Venus reporter, differentiation, iPSC, immune effectors, innate immune cells, mast cells, rapid protocol, stem cells, Animals, Cell Culture Techniques, Cell Differentiation, Cells, Cultured, GATA2 Transcription Factor, Genes, Reporter, Humans, Mast Cells, Mice, Mouse Embryonic Stem Cells, Peptide Hydrolases, Phenotype, Pluripotent Stem Cells, Receptors, Cell Surface