Comparative Analysis of Topological Patterns in Different Mammalian Networks

Hideyuki Okano (

Department of Physiology, Keio University School of Medicine


Induced pluripotent stem (iPS) cells are pluripotent stem cells directly reprogrammed from cultured mouse fibroblast by introducing Oct3/4, Sox2, c-Myc, and Klf4. Cells obtained using this technology, which allows the ethical issues and immunological rejection associated with embryonic stem (ES) cells to be avoided, might be a clinically useful source for cell replacement therapies. In our recent paper (Miura et al., Nat Biotech, 2009), we demonstrate that murine iPS cells formed neurospheres that produced electrophysiologically functional neurons, astrocytes, and oligodendrocytes. Secondary neurospheres (SNSs) generated from various mouse iPS cell showed their neural differentiation capacity and teratoma formation after transplantation into the brain of immunodeficient NOD/SCID mice. We found that origin (source of somatic cells) of the iPS cells are the crucial determinant for the potential tumorigenicity of iPS-derived neural stem/progenitor cells and that their tumorigenicity results from the persistent presence of undifferentiated cells within the SNSs. Surprisingly, SNSs derived from c-Myc minus iPS cells generated without drug selection showed robust tumorigenesis, in spite of their potential to contribute adult chimeric mice without tumor formation. The potential application of iPS-derived neural stem/progenitor cells for the regeneration of damaged CNS will be also discussed.

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Japanese Society for Bioinformatics