FGF signaling via MAPK is required early and improves Activin A-induced definitive endoderm formation from human embryonic stem cells |
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Authors: | Lina Sui Josué K MfopouMieke Geens Karen SermonLuc Bouwens |
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Institution: | a Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium b Department of Embryology and Genetics, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium |
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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. |
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Keywords: | AA Activin A Cyclo KAAD-cyclopamine DE definitive endoderm F FGF2 HBPI hepatocyte blockade and pancreas induction stage hESCs human embryonic stem cells LY LY294002 NG Noggin PNP PDX1- and NKX6 1-positive pancreatic progenitor PPP PDX1-positive pancreatic endoderm PS primitive streak RA retinoic acid SU SU5402 U U0126 |
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