Matsumoto Takuya, Fujimori Koki, Andoh-Noda Tomoko, Ando Takayuki, Kuzumaki Naoko, Toyoshima Manabu, Tada Hirobumi, Imaizumi Kent, Ishikawa Mitsuru, Yamaguchi Ryo, Isoda Miho, Zhou Zhi, Sato Shigeto, Kobayashi Tetsuro, Ohtaka Manami, Nishimura Ken, Kurosawa Hiroshi, Yoshikawa Takeo, Takahashi Takuya, Nakanishi Mahito, Ohyama Manabu, Hattori Nobutaka, Akamatsu Wado, Okano Hideyuki
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.
Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
Stem Cell Reports. 2016 Mar 8;6(3):422-35. doi: 10.1016/j.stemcr.2016.01.010. Epub 2016 Feb 18.
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.
利用源自患者体细胞的诱导多能干细胞（iPSC）对神经疾病进行建模，为阐明致病机制和进行药物筛选提供了一种手段。T细胞是患者特异性iPSC的理想来源，因为它们可以很容易地从样本中获得。最近的研究表明，iPSC保留了与它们起源细胞相关的表观遗传记忆，这限制了它们的分化潜能。通过胚状体形成进行分化的经典方法不适用于T细胞衍生的iPSC（TiPSC）。我们开发了一种基于神经球的稳健分化方案，尽管TiPSC与成人皮肤成纤维细胞衍生的iPSC之间存在全局基因表达差异，但该方案能使TiPSC分化为功能性神经元。此外，来自一名患有帕金森病的青少年患者的TiPSC衍生的神经元表现出几种帕金森病表型。因此，我们得出结论，TiPSC是对神经疾病进行建模的有用工具。
