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First published online 3 March 2004
doi: 10.1242/dev.01044
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1 The Carl C. Icahn Center for Gene Therapy and Molecular Medicine, Mount Sinai
School of Medicine, New York, NY 10029, USA
2 Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati,
OH 45229, USA
3 Department of Immunology, Medical Faculty/University Clinics, Ulm,
Germany
* Present address: Department of Public Health, Nara Medical University, Nara
634-8521, Japan
Present address: Paterson Institute for Cancer Research, Christie Hospital NHS
Trust, Wilmslow Road, Manchester M20 4BX, UK
Author for correspondence (e-mail:
gordon.keller{at}mssm.edu)
Accepted 3 December 2003
The cellular and molecular events regulating the induction and tissue-specific differentiation of endoderm are central to our understanding of the development and function of many organ systems. To define and characterize key components in this process, we have investigated the potential of embryonic stem (ES) cells to generate endoderm following their differentiation to embryoid bodies (EBs) in culture. We found that endoderm can be induced in EBs, either by limited exposure to serum or by culturing in the presence of activin A (activin) under serum-free conditions. By using an ES cell line with the green fluorescent protein (GFP) cDNA targeted to the brachyury locus, we demonstrate that endoderm develops from a brachyury+ population that also displays mesoderm potential. Transplantation of cells generated from activin-induced brachyury+ cells to the kidney capsule of recipient mice resulted in the development of endoderm-derived structures. These findings demonstrate that ES cells can generate endoderm in culture and, as such, establish this differentiation system as a unique murine model for studying the development and specification of this germ layer.
Key words: Stem cells, Endoderm
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