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Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12301-6. doi: 10.1073/pnas.0806522105. Epub 2008 Aug 21.

Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling.

Author information

1
Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom. davehay@talktalk.net

Abstract

Human embryonic stem cells (hESCs) are a valuable source of pluripotential primary cells. To date, however, their homogeneous cellular differentiation to specific cell types in vitro has proven difficult. Wnt signaling has been shown to play important roles in coordinating development, and we demonstrate that Wnt3a is differentially expressed at critical stages of human liver development in vivo. The essential role of Wnt3a in hepatocyte differentiation from hESCs is paralleled by our in vitro model, demonstrating the importance of a physiologic approach to cellular differentiation. Our studies provide compelling evidence that Wnt3a signaling is important for coordinated hepatocellular function in vitro and in vivo. In addition, we demonstrate that Wnt3a facilitates clonal plating of hESCs exhibiting functional hepatic differentiation. These studies represent an important step toward the use of hESC-derived hepatocytes in high-throughput metabolic analysis of human liver function.

PMID:
18719101
PMCID:
PMC2518825
DOI:
10.1073/pnas.0806522105
[Indexed for MEDLINE]
Free PMC Article

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