title: Functional Neurons Generated from T Cell-Derived Induced Pluripotent Stem Cells for Neurological Disease Modeling.
abstract: Modeling of neurological diseases using induced pluripotent stem cells (iPSCs) derived from the somatic cells of patients has provided a means of elucidating pathogenic mechanisms and performing drug screening. T cells are an ideal source of patient-specific iPSCs because they can be easily obtained from samples. Recent studies indicated that iPSCs retain an epigenetic memory relating to their cell of origin that restricts their differentiation potential. The classical method of differentiation via embryoid body formation was not suitable for T cell-derived iPSCs (TiPSCs). We developed a neurosphere-based robust differentiation protocol, which enabled TiPSCs to differentiate into functional neurons, despite differences in global gene expression between TiPSCs and adult human dermal fibroblast-derived iPSCs. Furthermore, neurons derived from TiPSCs generated from a juvenile patient with Parkinson's disease exhibited several Parkinson's disease phenotypes. Therefore, we conclude that TiPSCs are a useful tool for modeling neurological diseases.
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan; Institute for Innovation, Ajinomoto Co., Inc., Kawasaki-ku, Kanagawa 210-8681, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Fujimori
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan; Division of Medicine and Engineering Science, University of Yamanashi, Interdisciplinary Graduate School of Medicine and Engineering, Kofu, Yamanashi 400-8511, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Andoh-Noda
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ando
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan; Department of Pharmacology, Hoshi University, Pharmacy and Pharmaceutical Sciences, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Kuzumaki
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Toyoshima
authors.affiliation: Department of Physiology, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Kanagawa 236-0027, Japan.
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Tada
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Kent
authors.initials: K
authors.lastname: Imaizumi
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ishikawa
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan; Regenerative & Cellular Medicine Office, Sumitomo Dainippon Pharma Co., Ltd, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamaguchi
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan; Regenerative & Cellular Medicine Office, Sumitomo Dainippon Pharma Co., Ltd, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Isoda
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8431, Japan.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Dermatology, Keio University, School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan.
authors.forename: Manami
authors.initials: M
authors.lastname: Ohtaka
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan; Laboratory of Gene Regulation, University of Tsukuba, Faculty of Medicine, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Division of Medicine and Engineering Science, University of Yamanashi, Interdisciplinary Graduate School of Medicine and Engineering, Kofu, Yamanashi 400-8511, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kurosawa
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: Department of Physiology, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Kanagawa 236-0027, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan.
authors.forename: Mahito
authors.initials: M
authors.lastname: Nakanishi
authors.affiliation: Department of Dermatology, Keio University, School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Ohyama
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8431, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan; Center for Genomic and Regenerative Medicine, Juntendo University, School of Medicine, Bunkyo-ku, Tokyo 113-8431, Japan. Electronic address: awado@juntendo.ac.jp.
authors.forename: Wado
authors.initials: W
authors.lastname: Akamatsu
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: hidokano@a2.keio.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
mesh_terms: D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology*; D061251:Primary Cell Culture / Q000379:methods*; D013601:T-Lymphocytes / Q000166:cytology*