title: Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling.
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.
authors: Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom. davehay@talktalk.net
authors: David C
authors: DC
authors: Hay
authors: Judy
authors: J
authors: Fletcher
authors: Catherine
authors: C
authors: Payne
authors: John D
authors: JD
authors: Terrace
authors: Ronald C J
authors: RC
authors: Gallagher
authors: Jan
authors: J
authors: Snoeys
authors: James R
authors: JR
authors: Black
authors: Davina
authors: D
authors: Wojtacha
authors: Kay
authors: K
authors: Samuel
authors: Zara
authors: Z
authors: Hannoun
authors: Anne
authors: A
authors: Pryde
authors: Celine
authors: C
authors: Filippi
authors: Ian S
authors: IS
authors: Currie
authors: Stuart J
authors: SJ
authors: Forbes
authors: James A
authors: JA
authors: Ross
authors: Philip N
authors: PN
authors: Newsome
authors: John P
authors: JP
authors: Iredale
mesh_terms: D028341:Activins / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology*; D004707:Endoderm / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D022781:Hepatocytes / Q000637:transplantation; D006801:Humans; D008099:Liver / Q000166:cytology / Q000254:growth & development*; D051379:Mice; D016513:Mice, SCID; D013154:Spleen / Q000166:cytology; D014183:Transplantation, Heterologous; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*; D060508:Wnt3 Protein; D060509:Wnt3A Protein
chemical_list: C555510:WNT3A protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; C422405:activin A; D028341:Activins