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  • Recently several studies have suggested that peripheral


    Recently, several studies have suggested that peripheral blood mononuclear monooxygenase (PBMCs) are a promising resource for generating iPSCs because most of these cells do not undergo TCR rearrangement (Loh et al., 2010; Mack et al., 2011; Seki et al., 2010). However, PBMCs are composed of several cell types (e.g., T cells, B cells, and CD34 + progenitor cells), and each PBMC has an epigenetic memory of the cell from which it is derived. It is possible that PBMC-derived iPSCs restrict neural differentiation in a manner similar to TiPSCs. Since our present neural differentiation protocol was able to minimize the effect of cell origin, our protocol could be presumably applicable to iPSCs derived from other blood cell types. Here, we suggest that the method of neural induction is the most important factor in the study of neural cells derived from human TiPSCs. The optimized induction protocol allows various iPSC clones to differentiate into functional neuronal cells, regardless of the cell types from which they are derived. Therefore, TiPSCs can be used to study neurological diseases and to recapitulate disease-specific phenotypes, comparable with iPSCs derived from fibroblasts or other cells, when generated using the optimized differentiation protocol. We propose that T cells are an ideal source of patient-specific iPSCs and will be widely used for neurological disease modeling. We believe that our present neural differentiation protocol will minimize the effect of cell origin and is applicable to iPSCs derived from other tissues. For example, urine epithelial cells could be an excellent alternate source for the generation of iPSCs because monocytes without TCR rearrangement can also be obtained in a less invasive fashion (Song et al., 2011; Zhang et al., 2015; Zhou et al., 2011). These possibilities for modeling neurological diseases should be investigated in the future.
    Experimental Procedures
    Author Contributions
    Acknowledgments The authors thank Dr. Hajime Komano and all the members of H.O.’s laboratory for their encouragement and support. This work was supported by funding from the Project for the Realization of Regenerative Medicine and Support for Core Institutes for iPS Cell Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) to H.O., Research Center Network for Realization Research Centers/Projects of Regenerative Medicine (the Program for Intractable Disease Research utilizing disease-specific iPS Cells) from the Japan Science and Technology Agency (JST) and Japan Agency for Medical Research and Development (AMED) to H.O., the New Energy and Industrial Technology Development Organization (NEDO) to H.O. and W.A., the Japan Society for the Promotion of Science (JSPS) to W.A., and a Grant-in-Aid for the Global COE Program from MEXT to Keio University. H.O. is a scientific consultant for SanBio, Co. Ltd., Eisai, Co., Ltd.