title: Redefining definitive endoderm subtypes by robust induction of human induced pluripotent stem cells.
abstract: Many reports have described methods that induce definitive endoderm (DE) cells from human pluripotent stem cells (hPSCs). However, it is unclear whether the differentiation propensity of these DE cells is uniform. This uncertainty is due to the different developmental stages that give rise to anterior and posterior DE from anterior primitive streak (APS). Therefore, these DE cell populations might be generated from the different stages of APS cells, which affect the DE cell differentiation potential. Here, we succeeded in selectively differentiating early and late APS cells from human induced pluripotent stem cells (hiPSCs) using different concentrations of CHIR99021, a small molecule Wnt/β-catenin pathway activator. We also established novel differentiation systems from hiPSCs into three types of DE cells: anterior and posterior domains of anterior DE cells through early APS cells and posterior DE cells through late APS cells. These different DE cell populations could differentiate into distinct endodermal lineages in vitro, such as lung, liver or small intestine progenitors. These results indicate that different APS cells can produce distinct types of DE cells that have proper developmental potency and suggest a method to evaluate the quality of endodermal cell induction from hPSCs.
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Department of Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Matsuno
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Mae
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Okada
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Watanabe
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Toyoda
authors.affiliation: Department of Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Uchida
authors.affiliation: Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: osafu@cira.kyoto-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Osafune
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects; D004707:Endoderm / Q000187:drug effects / Q000254:growth & development*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects*; D007421:Intestine, Small / Q000254:growth & development; D008099:Liver / Q000254:growth & development; D008168:Lung / Q000254:growth & development; D011725:Pyridines / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000235:genetics
chemical_list: C473711:Chir 99021; D011725:Pyridines; D011743:Pyrimidines; D051176:beta Catenin
keywords: Anterior definitive endoderm; Directed differentiation; Late anterior primitive streak; Posterior definitive endoderm; iPSC