title: Derivation of pluripotent epiblast stem cells from mammalian embryos.
abstract: Although the first mouse embryonic stem (ES) cell lines were derived 25 years ago using feeder-layer-based blastocyst cultures, subsequent efforts to extend the approach to other mammals, including both laboratory and domestic species, have been relatively unsuccessful. The most notable exceptions were the derivation of non-human primate ES cell lines followed shortly thereafter by their derivation of human ES cells. Despite the apparent common origin and the similar pluripotency of mouse and human embryonic stem cells, recent studies have revealed that they use different signalling pathways to maintain their pluripotent status. Mouse ES cells depend on leukaemia inhibitory factor and bone morphogenetic protein, whereas their human counterparts rely on activin (INHBA)/nodal (NODAL) and fibroblast growth factor (FGF). Here we show that pluripotent stem cells can be derived from the late epiblast layer of post-implantation mouse and rat embryos using chemically defined, activin-containing culture medium that is sufficient for long-term maintenance of human embryonic stem cells. Our results demonstrate that activin/Nodal signalling has an evolutionarily conserved role in the derivation and the maintenance of pluripotency in these novel stem cells. Epiblast stem cells provide a valuable experimental system for determining whether distinctions between mouse and human embryonic stem cells reflect species differences or diverse temporal origins.
authors.affiliation: Department of Surgery and Cambridge Institute for Medical Research, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0XY, UK.
authors.forename: I Gabrielle M
authors.initials: IG
authors.lastname: Brons
authors.forename: Lucy E
authors.initials: LE
authors.lastname: Smithers
authors.forename: Matthew W B
authors.initials: MW
authors.lastname: Trotter
authors.forename: Peter
authors.initials: P
authors.lastname: Rugg-Gunn
authors.forename: Bowen
authors.initials: B
authors.lastname: Sun
authors.forename: Susana M
authors.initials: SM
authors.lastname: Chuva de Sousa Lopes
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Howlett
authors.forename: Amanda
authors.initials: A
authors.lastname: Clarkson
authors.forename: Lars
authors.initials: L
authors.lastname: Ahrlund-Richter
authors.forename: Roger A
authors.initials: RA
authors.lastname: Pedersen
authors.forename: Ludovic
authors.initials: L
authors.lastname: Vallier
mesh_terms: D028341:Activins / Q000378:metabolism; D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D003470:Culture Media / Q000737:chemistry; D010064:Embryo Implantation; D004622:Embryo, Mammalian / Q000166:cytology*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D020411:Oligonucleotide Array Sequence Analysis; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D015398:Signal Transduction
chemical_list: D003470:Culture Media; D028341:Activins