Naïve-like conversion enhances the difference in innate <i>in vitro</i> differentiation capacity between rabbit ES cells and iPS cells

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  • HONSHO Kimiko
    Organization for Promotion of Tenure Track, University of Miyazaki, Miyazaki 889-1692, Japan
  • HIROSE Michiko
    RIKEN BioResource Center, Ibaraki 305-0074, Japan
  • HATORI Masanori
    RIKEN BioResource Center, Ibaraki 305-0074, Japan
  • YASMIN Lubna
    Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Ibaraki 305-0843, Japan
  • IZU Haruna
    Organization for Promotion of Tenure Track, University of Miyazaki, Miyazaki 889-1692, Japan
  • MATOBA Shogo
    RIKEN BioResource Center, Ibaraki 305-0074, Japan Present: Harvard Medical School, Boston, MA 02115, USA
  • TOGAYACHI Sumie
    RIKEN BioResource Center, Ibaraki 305-0074, Japan
  • MIYOSHI Hiroyuki
    RIKEN BioResource Center, Ibaraki 305-0074, Japan
  • SANKAI Tadashi
    Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Ibaraki 305-0843, Japan
  • OGURA Atsuo
    RIKEN BioResource Center, Ibaraki 305-0074, Japan
  • HONDA Arata
    Organization for Promotion of Tenure Track, University of Miyazaki, Miyazaki 889-1692, Japan RIKEN BioResource Center, Ibaraki 305-0074, Japan

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  • Naive-like conversion enhances the difference in innate in vitro differentiation capacity between rabbit ES cells and iPS cells
  • Naïve-like conversion enhances the difference in innate in vitro differentiation capacity between rabbit ES cells and iPS cells

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Abstract

Quality evaluation of pluripotent stem cells using appropriate animal models needs to be improved for human regenerative medicine. Previously, we demonstrated that although the in vitro neural differentiating capacity of rabbit induced pluripotent stem cells (iPSCs) can be mitigated by improving their baseline level of pluripotency, i.e., by converting them into the so-called “naïve-like” state, the effect after such conversion of rabbit embryonic stem cells (ESCs) remains to be elucidated. Here we found that naïve-like conversion enhanced the differences in innate in vitro differentiation capacity between ESCs and iPSCs. Naïve-like rabbit ESCs exhibited several features indicating pluripotency, including the capacity for teratoma formation. They differentiated into mature oligodendrocytes much more effectively (3.3–7.2 times) than naïve-like iPSCs. This suggests an inherent variation in differentiation potential in vitro among PSC lines. When naïve-like ESCs were injected into preimplantation rabbit embryos, although they contributed efficiently to forming the inner cell mass of blastocysts, no chimeric pups were obtained. Thus, in vitro neural differentiation following naïve-like conversion is a promising option for determining the quality of PSCs without the need to demonstrate chimeric contribution. These results provide an opportunity to evaluate which pluripotent stem cells or treatments are best suited for therapeutic use.

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