title: FGF signaling via MAPK is required early and improves Activin A-induced definitive endoderm formation from human embryonic stem cells.
abstract: Considering their unlimited proliferation and pluripotency properties, human embryonic stem cells (hESCs) constitute a promising resource applicable for cell replacement therapy. To facilitate this clinical translation, it is critical to study and understand the early stage of hESCs differentiation wherein germ layers are defined. In this study, we examined the role of FGF signaling in Activin A-induced definitive endoderm (DE) differentiation in the absence of supplemented animal serum. We found that activated FGF/MAPK signaling is required at the early time point of Activin A-induced DE formation. In addition, FGF activation increased the number of DE cells compared to Activin A alone. These DE cells could further differentiate into PDX1 and NKX6.1 positive pancreatic progenitors in vitro. We conclude that Activin A combined with FGF/MAPK signaling efficiently induce DE cells in the absence of serum. These findings improve our understanding of human endoderm formation, and constitute a step forward in the generation of clinical grade hESCs progenies for cell therapy.
authors.affiliation: Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium. linasui@vub.ac.be
authors.forename: Lina
authors.initials: L
authors.lastname: Sui
authors.forename: Josué K
authors.initials: JK
authors.lastname: Mfopou
authors.forename: Mieke
authors.initials: M
authors.lastname: Geens
authors.forename: Karen
authors.initials: K
authors.lastname: Sermon
authors.forename: Luc
authors.initials: L
authors.lastname: Bouwens
mesh_terms: D028341:Activins / Q000494:pharmacology*; D002452:Cell Count; D002460:Cell Line; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects*; D004707:Endoderm / Q000166:cytology*; D005346:Fibroblast Growth Factors / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016895:Culture Media, Serum-Free; C422405:activin A; D028341:Activins; D005346:Fibroblast Growth Factors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020929:Mitogen-Activated Protein Kinase Kinases