Nature Biotechnology
- 24, 1402 - 1411 (2006)
Published online: 5 November 2006; | doi:10.1038/nbt1258
BMP-4 is required for hepatic specification of mouse embryonic stem cell–derived definitive endodermValerie Gouon-Evans1, Lise Boussemart1, Paul Gadue1, Dirk Nierhoff2, 3, Christoph I Koehler2, Atsushi Kubo4, David A Shafritz2 & Gordon Keller11
Department of Gene and Cell Medicine, Black Family Stem Cell Institute, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, New York 10029, USA. 2
Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, New York 10461, USA. 3
Department of Gastroenterology and Hepatology, University of Cologne, Germany. 4
Present address: First Department of Internal Medicine, Nara Medical University, Nara 634-8521, Japan (A.K.).
Correspondence should be addressed to Gordon Keller gordon.keller@mssm.edu When differentiated in the presence of activin A in serum-free conditions, mouse embryonic stem cells efficiently generate an endoderm progenitor population defined by the coexpression of either Brachyury, Foxa2 and c-Kit, or c-Kit and Cxcr4. Specification of these progenitors with bone morphogenetic protein-4 in combination with basic fibroblast growth factor and activin A results in the development of hepatic populations highly enriched (45–70%) for cells that express the  -fetoprotein and albumin proteins. These cells also express transcripts of Afp, Alb1, Tat, Cps1, Cyp7a1 and Cyp3a11; they secrete albumin, store glycogen, show ultrastructural characteristics of mature hepatocytes, and are able to integrate into and proliferate in injured livers in vivo and mature into hepatocytes expressing dipeptidyl peptidase IV or fumarylacetoacetate hydrolase. Together, these findings establish a developmental pathway in embryonic stem cell differentiation cultures that leads to efficient generation of cells with an immature hepatocytic phenotype.
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15 mm dishes (Falcon)
m nylon mesh (Sefar America)
