title: Two-step differentiation of mast cells from induced pluripotent stem cells.
abstract: Mast cells play important roles in the pathogenesis of allergic diseases. They are generally classified into 2 phenotypically distinct populations: connective tissue-type mast cells (CTMCs) and mucosal-type mast cells (MMCs). The number of mast cells that can be obtained from tissues is limited, making it difficult to study the function of mast cells. Here, we report the generation and characterization of CTMC-like mast cells derived from mouse induced pluripotent stem (iPS) cells. iPS cell-derived mast cells (iPSMCs) were generated by the OP9 coculture method or embryoid body formation method. The number of Safranin O-positive cells, expression levels of CD81 protein and histidine decarboxylase mRNA, and protease activities were elevated in the iPSMCs differentiated by both methods as compared with those in bone marrow-derived mast cells (BMMCs). Electron microscopic analysis revealed that iPSMCs contained more granules than BMMCs. Degranulation was induced in iPSMCs after stimulation with cationic secretagogues or vancomycin. In addition, iPSMCs had the ability to respond to stimulation with the IgE/antigen complex in vitro and in vivo. Moreover, when iPSMCs generated on OP9 cells were cocultured with Swiss 3T3 fibroblasts, protease activities as maturation index were more elevated, demonstrating that mature mast cells were differentiated from iPS cells. iPSMCs can be used as an in vitro model of CTMCs to investigate their functions.
authors.affiliation: Laboratory of Stem Cell Regulation, National Institute of Biomedical Innovation, Osaka, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Tashiro
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Sumie
authors.initials: S
authors.lastname: Katayama
authors.forename: Waka
authors.initials: W
authors.lastname: Ishida
authors.forename: Ken
authors.initials: K
authors.lastname: Fukuda
authors.forename: Atsuki
authors.initials: A
authors.lastname: Fukushima
authors.forename: Ryoko
authors.initials: R
authors.lastname: Araki
authors.forename: Masumi
authors.initials: M
authors.lastname: Abe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawabata
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015550:Cell Degranulation; D002454:Cell Differentiation; D002460:Cell Line; D003239:Connective Tissue Cells / Q000166:cytology*; D006640:Histidine Decarboxylase / Q000235:genetics; D007073:Immunoglobulin E / Q000276:immunology; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010323:Passive Cutaneous Anaphylaxis; D010619:Phenazines / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060225:Tetraspanin 28 / Q000235:genetics; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D010619:Phenazines; D012333:RNA, Messenger; D060225:Tetraspanin 28; D007073:Immunoglobulin E; D014640:Vancomycin; D006640:Histidine Decarboxylase; C009195:safranine T