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| Derivation of pluripotent epiblast stem cells from mammalian embryos |
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| Author(s): Brons IGM (Brons, I. Gabrielle M.), Smithers LE (Smithers, Lucy E.), Trotter MWB (Trotter, Matthew W. B.), Rugg-Gunn P (Rugg-Gunn, Peter), Sun BW (Sun, Bowen), Lopes SMCD (de Sousa Lopes, Susana M. Chuva), Howlett SK (Howlett, Sarah K.), Clarkson A (Clarkson, Amanda), Ahrlund-Richter L (Ahrlund-Richter, Lars), Pedersen RA (Pedersen, Roger A.), Vallier L (Vallier, Ludovic) |
| Source: NATURE Volume: 448 Issue: 7150 Pages: 191-U7 Published: JUL 12 2007 |
| Times Cited: 138 References: 26 |
| Abstract: Although the first mouse embryonic stem (ES) cell lines were derived 25 years ago(1,2) 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(3) followed shortly thereafter by their derivation of human ES cells(4). 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Vallier, L (reprint author), Univ Cambridge, Addenbrookes Hosp, Dept Surg, Cambridge CB2 0XY, England |
Addresses:
1. Univ Cambridge, Addenbrookes Hosp, Dept Surg, Cambridge CB2 0XY, England
2. Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge CB2 0XY, England
3. UCL, Wolfson Inst Biomed Res, CR UK Viral Oncol Grp, London WC1E 6BT, England
4. Univ Cambridge, Wellcome Trust Canc Res UK, Gurdon Inst Canc & Dev Biol, Cambridge CB2 1QR, England
5. Univ Cambridge, Dept Physiol, Cambridge CB2 1QR, England
6. Univ Cambridge, Juvenile Diabet Res Fdn, Wellcome Trust Diabet & Inflammat Lab, Cambridge CB2 0XY, England
7. Univ Cambridge, Hosp NHS Fdn Trust, Dept Med Genet, Cambridge CB2 2FF, England
8. Karolinska Inst, Karolinska Univ Hosp, Clin Res Ctr, Dept Lab Med, S-14157 Stockholm, Sweden |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 188QN |
| ISSN: 0028-0836 |
| DOI: 10.1038/nature05950 |
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