title: Cynomolgus monkey induced pluripotent stem cells established by using exogenous genes derived from the same monkey species.
abstract: Induced pluripotent stem (iPS) cells established by introduction of the transgenes POU5F1 (also known as Oct3/4), SOX2, KLF4 and c-MYC have competence similar to embryonic stem (ES) cells. iPS cells generated from cynomolgus monkey somatic cells by using genes taken from the same species would be a particularly important resource, since various biomedical investigations, including studies on the safety and efficacy of drugs, medical technology development, and research resource development, have been performed using cynomolgus monkeys. In addition, the use of xenogeneic genes would cause complicating matters such as immune responses when they are expressed. In this study, therefore, we established iPS cells by infecting cells from the fetal liver and newborn skin with amphotropic retroviral vectors containing cDNAs for the cynomolgus monkey genes of POU5F1, SOX2, KLF4 and c-MYC. Flat colonies consisting of cells with large nuclei, similar to those in other primate ES cell lines, appeared and were stably maintained. These cell lines had normal chromosome numbers, expressed pluripotency markers and formed teratomas. We thus generated cynomolgus monkey iPS cell lines without the introduction of ecotropic retroviral receptors or other additional transgenes by using the four allogeneic transgenes. This may enable detailed analysis of the mechanisms underlying the reprogramming. In conclusion, we showed that iPS cells could be derived from cynomolgus monkey somatic cells. To the best of our knowledge, this is the first report on iPS cell lines established from cynomolgus monkey somatic cells by using genes from the same species.
authors.affiliation: Tsukuba Primate Research Center (TPRC), National Institute of Biomedical Innovation (NIBIO), 1-1 Hachimandai, Tsukuba, Ibaraki 305-0843, Japan. shimo@nibio.go.jp
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Shimozawa
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Ono
authors.forename: Manami
authors.initials: M
authors.lastname: Shimada
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shibata
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takahashi
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Inada
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Takada
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nosaka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yasutomi
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002469:Cell Separation; D053595:Embryonic Stem Cells / Q000166:cytology*; D016259:Genes, myc / Q000235:genetics; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D008252:Macaca fascicularis; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics; D013724:Teratoma / Q000235:genetics / Q000378:metabolism; D019076:Transgenes / Q000235:genetics
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D050814:Octamer Transcription Factor-3; D055748:SOXB1 Transcription Factors
keywords: Cynomolgus monkey; Cynomolgus monkey genes; Induced pluripotent stem cells; Medical research; Non-human primate