title: The inhibitory role of stromal cell mesenchyme on human embryonic stem cell hepatocyte differentiation is overcome by Wnt3a treatment.
abstract: Pluripotent stem cells are derived from the inner cell mass of preimplantation embryos, and display the ability of the embryonic founder cells by forming all three germ lineages in vitro. It is well established that the cellular niche plays an important role in stem cell maintenance and differentiation. Stem cells generally have limited function without the specialized microenvironment of the niche that provides key cell-cell contact, soluble mediators, and extracellular matrices. We were interested in the role that Wnt signaling, in particular Wnt3a, played in human embryonic stem cell (hESC) differentiation to hepatic endoderm in vitro. hESC differentiation to hepatic endoderm was efficient in pure stem cell populations. However, in younger hESC lines, generating stromal cell mesenchyme, our model was very inefficient. The negative effect of stroma could be reversed by pretreating hESCs with Wnt3a prior to the onset of hepatocyte differentiation. Wnt3a pretreatment reinstated efficient hESC differentiation to hepatic endoderm. These studies represent an important step in understanding hepatocyte differentiation from hESCs and the role played by the cellular niche in vitro.
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Judy
authors.initials: J
authors.lastname: Fletcher
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.forename: Kay
authors.initials: K
authors.lastname: Samuel
authors.forename: James R
authors.initials: JR
authors.lastname: Black
authors.forename: Zara
authors.initials: Z
authors.lastname: Hannoun
authors.forename: Ian S
authors.initials: IS
authors.lastname: Currie
authors.forename: John D
authors.initials: JD
authors.lastname: Terrace
authors.forename: Catherine
authors.initials: C
authors.lastname: Payne
authors.forename: Celine
authors.initials: C
authors.lastname: Filippi
authors.forename: Philip
authors.initials: P
authors.lastname: Newsome
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Forbes
authors.forename: James A
authors.initials: JA
authors.lastname: Ross
authors.forename: John P
authors.initials: JP
authors.lastname: Iredale
authors.forename: David C
authors.initials: DC
authors.lastname: Hay
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060508:Wnt3 Protein; D060509:Wnt3A Protein
chemical_list: C555510:WNT3A protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein