title: Enucleated ovine oocyte supports human somatic cells reprogramming back to the embryonic stage.
abstract: Increased possibility of universality of ooplasmic reprogramming factors resulted in a parallel increased interest to use interspecies somatic cell nuclear transfer (iSCNT) to address basic questions of developmental biology and to improve the feasibility of cell therapy. In this study, the interactions between human somatic cells and ovine oocytes were investigated. Nuclear remodeling events were first observed 3 h post-iSCNT as nuclear swelling, chromosome condensation, and spindle formation. A time-dependent decrease in maturation promoting activity of inactivated reconstructs coincided with increased aberrations in chromosome and spindle organization of the newly developed embryos. The sequence and duration of nuclear remodeling events were irrespective of donor cell type used. Although the majority of the reconstituted embryos arrested before embryonic genome activation (8-16-cell) stage, less than 5% of them could progress beyond transcription-requiring developmental stage and formed blastocyst-like structures with distinct inner cell mass and trophectoderm at days 7 and 8 post-SCNT. Importantly, real-time assessment of three developmentally important genes (Oct4, Sox2, and Nanog) indicated their upregulation in iSCNT blastocysts. Blastocyst-derived outgrowths had alkaline phosphatase activity that was lost upon passage. Collectively, this study introduced ovine oocyte as a credible cytoplast for remodeling and reprogramming of human somatic cells back to the embryonic stage and provided a platform for further studies to unravel possible differences exist between reprogramming ability of oocytes of different mammalian species.
authors.affiliation: Department of Reproduction and Development, Reproductive Biomedicine Research Center, Royan Institute for Animal Biotechnology, ACECR, Isfahan, Iran.
authors.forename: S Morteza
authors.initials: SM
authors.lastname: Hosseini
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hajian
authors.forename: Mohsen
authors.initials: M
authors.lastname: Forouzanfar
authors.forename: Fariba
authors.initials: F
authors.lastname: Moulavi
authors.forename: Parvaneh
authors.initials: P
authors.lastname: Abedi
authors.forename: Vajiheh
authors.initials: V
authors.lastname: Asgari
authors.forename: Somayyeh
authors.initials: S
authors.lastname: Tanhaei
authors.forename: Hassan
authors.initials: H
authors.lastname: Abbasi
authors.forename: Farnoosh
authors.initials: F
authors.lastname: Jafarpour
authors.forename: Soamyyeh
authors.initials: S
authors.lastname: Ostadhosseini
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Karamali
authors.forename: Khadijeh
authors.initials: K
authors.lastname: Karbaliaie
authors.forename: Hossein
authors.initials: H
authors.lastname: Baharvand
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Nasr-Esfahani
mesh_terms: D000328:Adult; D000818:Animals; D054337:Cell Dedifferentiation / Q000235:genetics / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics / Q000502:physiology*; D019976:Cloning, Organism / Q000379:methods; D054885:Cumulus Cells / Q000166:cytology / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006801:Humans; D008297:Male; D053652:Nuclear Transfer Techniques; D009865:Oocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D034561:Sheep, Domestic; D014183:Transplantation, Heterologous