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

• Main Authors: Takuya Matsumoto, Koki Fujimori, Tomoko Andoh-Noda, Takayuki Ando, Naoko Kuzumaki, Manabu Toyoshima, Hirobumi Tada, Kent Imaizumi, Mitsuru Ishikawa, Ryo Yamaguchi, Miho Isoda, Zhi Zhou, Shigeto Sato, Tetsuro Kobayashi, Manami Ohtaka, Ken Nishimura, Hiroshi Kurosawa, Takeo Yoshikawa, Takuya Takahashi, Mahito Nakanishi, Manabu Ohyama, Nobutaka Hattori, Wado Akamatsu, Hideyuki Okano
• Format: Article
• Language: English
• Published: Elsevier 2016-03-01
• Series: Stem Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2213671116000278

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.