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

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    Rights statement: Freely available online through the PNAS open access option. © 2008 by The National Academy of Sciences of the USA

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http://www.pnas.org/content/105/34/12301
Original languageEnglish
Pages (from-to)12301-12306
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume105
Issue number34
DOIs
Publication statusPublished - 26 Aug 2008

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.

    Research areas

  • definitive endoderm, function, hepatocyte, drug metabolism, high throughput

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