Derivation of pluripotent epiblast stem cells from mammalian embryos

• Published in: Nature Vol. 448; no. 7150; pp. 191 - 195
• Main Authors: Trotter, Matthew W. B, Howlett, Sarah K, Sun, Bowen, Clarkson, Amanda, Smithers, Lucy E, Pedersen, Roger A, Brons, I. Gabrielle M, Ahrlund-Richter, Lars, Rugg-Gunn, Peter, Chuva de Sousa Lopes, Susana M, Vallier, Ludovic
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 12.07.2007; Nature Publishing Group
• Subjects: Activins - metabolism; Analysis; Animal models in research; Animals; Biological and medical sciences; Cell culture; Cell Culture Techniques; Cell death; Cell differentiation, maturation, development, hematopoiesis; Cell Line; Cell physiology; Culture; Culture Media - chemistry; Derivation; DNA microarrays; Embryo Implantation; Embryo, Mammalian - cytology; Embryology; Embryonic Stem Cells - cytology; Embryonic Stem Cells - metabolism; Embryos; Evaluation; Evolutionary biology; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Human; Humans; Leukemia; Maintenance; Male; Mammals; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Molecular and cellular biology; Oligonucleotide Array Sequence Analysis; Origins; Pluripotent Stem Cells - cytology; Pluripotent Stem Cells - metabolism; Primates; Rats; Rats, Sprague-Dawley; Rats, Wistar; Rodents; Signal Transduction; Signalling; Stem cell research; Stem cells; Human; Vertebrata; Embryo; Mammalia; Mouse; Pluripotent cell; Stem cell; Rodentia
• ISSN: 0028-0836; 1476-4687; 1476-4687; 1476-4679
• DOI: 10.1038/nature05950

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.