title: Recombinant Laminins Drive the Differentiation and Self-Organization of hESC-Derived Hepatocytes.
abstract: Stem cell-derived somatic cells represent an unlimited resource for basic and translational science. Although promising, there are significant hurdles that must be overcome. Our focus is on the generation of the major cell type of the human liver, the hepatocyte. Current protocols produce variable populations of hepatocytes that are the product of using undefined components in the differentiation process. This serves as a significant barrier to scale-up and application. To tackle this issue, we designed a defined differentiation process using recombinant laminin substrates to provide instruction. We demonstrate efficient hepatocyte specification, cell organization, and significant improvements in cell function and phenotype. This is driven in part by the suppression of unfavorable gene regulatory networks that control cell proliferation and migration, pluripotent stem cell self-renewal, and fibroblast and colon specification. We believe that this represents a significant advance, moving stem cell-based hepatocytes closer toward biomedical application.
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Cameron
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
authors.forename: Rosanne
authors.initials: R
authors.lastname: Tan
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology eV-Hans-Knöll Institute, 07743 Jena, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schmidt-Heck
authors.affiliation: IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Ardeystraße 67, 44139 Dortmund, Germany.
authors.forename: Gisela
authors.initials: G
authors.lastname: Campos
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Lyall
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
authors.forename: Baltasar
authors.initials: B
authors.lastname: Lucendo-Villarin
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
authors.forename: Dagmara
authors.initials: D
authors.lastname: Szkolnicka
authors.affiliation: Faculty of Life Sciences, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Bates
authors.affiliation: Faculty of Life Sciences, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Kimber
authors.affiliation: IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Ardeystraße 67, 44139 Dortmund, Germany.
authors.forename: Jan G
authors.initials: JG
authors.lastname: Hengstler
authors.affiliation: IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Ardeystraße 67, 44139 Dortmund, Germany.
authors.forename: Patricio
authors.initials: P
authors.lastname: Godoy
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Forbes
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK. Electronic address: davehay@talktalk.net.
authors.forename: David C
authors.initials: DC
authors.lastname: Hay
mesh_terms: D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D053263:Gene Regulatory Networks; D015894:Genome, Human; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D007797:Laminin; D011994:Recombinant Proteins