title: Naïve-like conversion enhances the difference in innate in vitro differentiation capacity between rabbit ES cells and iPS cells.
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.
authors.affiliation: Organization for Promotion of Tenure Track, University of Miyazaki, Miyazaki 889-1692, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Honsho
authors.forename: Michiko
authors.initials: M
authors.lastname: Hirose
authors.forename: Masanori
authors.initials: M
authors.lastname: Hatori
authors.forename: Lubna
authors.initials: L
authors.lastname: Yasmin
authors.forename: Haruna
authors.initials: H
authors.lastname: Izu
authors.forename: Shogo
authors.initials: S
authors.lastname: Matoba
authors.forename: Sumie
authors.initials: S
authors.lastname: Togayachi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Sankai
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ogura
authors.forename: Arata
authors.initials: A
authors.lastname: Honda
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D003584:Cytological Techniques; D053595:Embryonic Stem Cells / Q000166:cytology*; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D051379:Mice; D016513:Mice, SCID; D009474:Neurons / Q000473:pathology; D009836:Oligodendroglia / Q000166:cytology; D016133:Polymerase Chain Reaction; D011817:Rabbits; D013724:Teratoma / Q000378:metabolism
chemical_list: D049452:Green Fluorescent Proteins; D000469:Alkaline Phosphatase