title: Differentiation of induced pluripotent stem cells to thymic epithelial cells by phenotype.
abstract: Thymic epithelial cells (TECs) are present in both cortical and medullary thymic areas, and have crucial roles in functional T-cell development. In this study, we studied the differentiation of induced pluripotent stem cells (iPSCs) to TEC. When iPSC were cultured for 4 days in collagen IV-coated dishes in the presence of both activin A and lithium chloride (LiCl), the cells differentiated to definitive endoderm through mesendoderm. Further treatment with Fgf8 followed by Fgf7, Fgf10 and BMP4 differentiated iPSC to thymic epithelial progenitor cells (TEPCs) by phenotype. Gene expression of Hoxa3, Pax1 and Pax9 was observed and cell surface proteins EpCAM1 and MTS24 were detected at day 14 of iPSC differentiation. TEPCs differentiated to medullary TECs (mTECs) by phenotype following the addition of receptor activator nuclear factor B ligand with LiCl. Thus, we successfully induced efficient differentiation from mouse iPSC to TEPCs and mTEC by phenotype using chemically defined conditions.
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Inami
authors.forename: Tohru
authors.initials: T
authors.lastname: Yoshikai
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ito
authors.forename: Naomi
authors.initials: N
authors.lastname: Nishio
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Suzuki
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Sakurai
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Isobe
mesh_terms: D028341:Activins / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004707:Endoderm / Q000166:cytology; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology; D051379:Mice; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology*
chemical_list: D012333:RNA, Messenger; C422405:activin A; D028341:Activins; D018021:Lithium Chloride