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Stem Cell Reports. 2016 Mar 8;6(3):422-35. doi: 10.1016/j.stemcr.2016.01.010. Epub 2016 Feb 18.

Functional Neurons Generated from T Cell-Derived Induced Pluripotent Stem Cells for Neurological Disease Modeling.

Author information

1
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.
2
Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
3
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.
4
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.
5
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
6
Department of Physiology, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Kanagawa 236-0027, Japan.
7
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.
8
Department of Neurology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8431, Japan.
9
Department of Dermatology, Keio University, School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
10
Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan.
11
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.
12
Division of Medicine and Engineering Science, University of Yamanashi, Interdisciplinary Graduate School of Medicine and Engineering, Kofu, Yamanashi 400-8511, Japan.
13
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.
14
Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: hidokano@a2.keio.jp.

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.

PMID:
26905201
PMCID:
PMC4788773
DOI:
10.1016/j.stemcr.2016.01.010
[Indexed for MEDLINE]
Free PMC Article

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