title: Interspecies chimera between primate embryonic stem cells and mouse embryos: monkey ESCs engraft into mouse embryos, but not post-implantation fetuses.
abstract: Unequivocal evidence for pluripotency in which embryonic stem cells contribute to chimeric offspring has yet to be demonstrated in human or nonhuman primates (NHPs). Here, rhesus and baboons ESCs were investigated in interspecific mouse chimera generated by aggregation or blastocyst injection. Aggregation chimera produced mouse blastocysts with GFP-nhpESCs at the inner cell mass (ICM), and embryo transfers (ETs) generated dimly-fluorescencing abnormal fetuses. Direct injection of GFP-nhpESCs into blastocysts produced normal non-GFP-fluorescencing fetuses. Injected chimera showed >70% loss of GFP-nhpESCs after 21 h culture. Outgrowths of all chimeric blastocysts established distinct but separate mouse- and NHP-ESC colonies. Extensive endogenous autofluorescence compromised anti-GFP detection and PCR analysis did not detect nhpESCs in fetuses. NhpESCs localize to the ICM in chimera and generate pregnancies. Because primate ESCs do not engraft post-implantation, and also because endogenous autofluorescence results in misleading positive signals, interspecific chimera assays for pluripotency with primate stem cells is unreliable with the currently available ESCs. Testing primate ESCs reprogrammed into even more naïve states in these inter-specific chimera assays will be an important future endeavor.
authors.affiliation: Division of Developmental and Regenerative Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh Development Center, Magee-Womens Research Institute and Foundation, 204 Craft Avenue, Pittsburgh, PA, USA.
authors.forename: Calvin
authors.initials: C
authors.lastname: Simerly
authors.forename: Dave
authors.initials: D
authors.lastname: McFarland
authors.forename: Carlos
authors.initials: C
authors.lastname: Castro
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Lin
authors.forename: Carrie
authors.initials: C
authors.lastname: Redinger
authors.forename: Ethan
authors.initials: E
authors.lastname: Jacoby
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Mich-Basso
authors.forename: Kyle
authors.initials: K
authors.lastname: Orwig
authors.forename: Parker
authors.initials: P
authors.lastname: Mills
authors.forename: Eric
authors.initials: E
authors.lastname: Ahrens
authors.forename: Chris
authors.initials: C
authors.lastname: Navara
authors.forename: Gerald
authors.initials: G
authors.lastname: Schatten
mesh_terms: D000818:Animals; D002678:Chimera / Q000196:embryology*; D010064:Embryo Implantation; D004624:Embryo Transfer; D004622:Embryo, Mammalian / Q000166:cytology; D053595:Embryonic Stem Cells / Q000166:cytology*; D005260:Female; D000882:Haplorhini / Q000196:embryology*; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy