title: Behavior of leucine-rich repeat-containing G-protein coupled receptor 5-expressing cells in the reprogramming process.
abstract: It remains unclear what cells are proper for the generation of induced pluripotent stem cells (iPSCs). Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is well known as a tissue stem cell and progenitor marker, both of which are reported to be sensitive to reprogramming. In the present study, we examined the reprogramming behavior of Lgr5-expressing cells (Lgr5+ cells). First, we compared reprogramming behavior using mouse Lgr5+ and Lgr5 negative (Lgr5-) hair follicles (HFs). The number of alkaline phosphatase staining-positive cells was lesser in a well of Lgr5+ HFs than in Lgr5- HFs; however, the ratio of Nanog+ SSEA1+ cells in the cell mixture derived from Lgr5+ HFs was much higher than that from Lgr5- HFs. Lgr5+ cells could be induced from mouse embryonic fibroblasts (MEFs) after transduction with Yamanaka factors. As shown in HFs, the progeny of Lgr5+ cells arising from MEFs highly converted into Nanog+ cells and did not form Nanog- colonies. The progeny represented the status of the late reprogramming phase to a higher degree than the nonprogeny. We also confirmed this using human Lg5+ cells. Our findings suggest that the use of Lgr5+ cells will minimize sorting efforts for obtaining superior iPSCs.
authors.affiliation: Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan; Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. Electronic address: ariokay@med.nagoya-u.ac.jp.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Arioka
authors.affiliation: Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ito
authors.affiliation: Division of Animal Experiment, Life Science Research Center, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hirata
authors.affiliation: Department of Life Science Frontiers, Center for iPS Cell Research and Applicaion (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Semi
authors.affiliation: Department of Life Science Frontiers, Center for iPS Cell Research and Applicaion (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Seishima
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D065150:Cellular Reprogramming; D058732:Embryoid Bodies / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D007930:Leucine / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D000071317:Nanog Homeobox Protein / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C116884:LGR5 protein, human; D000071317:Nanog Homeobox Protein; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D014157:Transcription Factors; D007930:Leucine
keywords: Cell reprogramming; Induced pluripotent stem cells; Leucine-rich repeat-containing G-protein coupled receptor 5