FGF signaling via MAPK is required early and improves Activin A-induced definitive endoderm formation from human embryonic stem cells

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• 作者：Lina Sui ; Josu¨¦ K. Mfopou ; Mieke Geens ; Karen Sermon ; Luc Bouwens
• 关键词：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-
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 出版时间：28 September, 2012
• 年：2012
• 卷：426
• 期：3
• 页码：380-385
• 全文大小：1448 K

文摘

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.