Direct development of functionally mature tryptase/chymase double-positive connective tissue-type mast cells from primate embryonic stem cells.
Conditions that influence the selective development or recruitment of connective tissue-type and mucosal-type mast cells (MCs) are not well understood. Here, we report that cynomolgus monkey embryonic stem (ES) cells cocultured with the murine aorta-gonad-mesonephros-derived stromal cell line AGM-S1 differentiated into cobblestone (CS)-like cells by day 10-15. When replated onto fresh AGM-S1 with the addition of stem cell factor, interleukin-6, and Flt3 ligand, these CS-like cells displayed robust growth and generated almost 100% tryptase/chymase double-positive MCs within 3 weeks. At all time points, the percentage of tryptase-positive cells did not exceed that of chymase-positive cells. These ES-derived MCs were CD45+/Kit+/CD31+/CD203c+/HLA-DR- and coexpressed a high-affinity IgE receptor on their surface, which was upregulated after IgE exposure. Electron microscopy showed that they contained many electron dense granules. Moreover, ES-derived MCs responded to stimulation by via IgE and substance P by releasing histamine. These results indicate that ES-derived MCs have the phenotype of functionally mature connective tissue-type MCs. The rapid maturation of ES-derived MCs suggests a unique embryonic pathway in primates for early development of connective tissue-type MCs, which may be independent from the developmental pathway of mucosal-type MCs.
Ma
Feng
F
Department of Pediatrics, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Kambe
Naotomo
N
Wang
Dan
D
Shinoda
Gen
G
Fujino
Hisanori
H
Umeda
Katsutsugu
K
Fujisawa
Akihiro
A
Ma
Lina
L
Suemori
Hirofumi
H
Nakatsuji
Norio
N
Miyachi
Yoshiki
Y
Torii
Ryuzo
R
Tsuji
Kohichiro
K
Heike
Toshio
T
Nakahata
Tatsutoshi
T
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D053818:Chymases / Q000378:metabolism*; D018920:Coculture Techniques / Q000379:methods*; D016207:Cytokines / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D006632:Histamine / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects; D010641:Phenotype; D011323:Primates; D013373:Substance P / Q000378:metabolism; D053802:Tryptases / Q000378:metabolism*
D016207:Cytokines; D013373:Substance P; D007073:Immunoglobulin E; D006632:Histamine; D053818:Chymases; D053802:Tryptases