Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium.
Biochem Biophys Res Commun. 2012 Sep 28;426(3):380-5. doi: 10.1016/j.bbrc.2012.08.098. Epub 2012 Aug 29.
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.
考虑到其无限增殖和多能性特性，人类胚胎干细胞（hESCs）构成了一种有前途的资源，可适用于细胞替代治疗。为了促进这种临床转化，研究和了解定义胚层的 hESC 分化的早期阶段至关重要。在这项研究中，我们研究了 FGF 信号在激活素 A 诱导的确定性内胚层（DE）分化中的作用，而无需补充动物血清。我们发现，在激活素 A 诱导的 DE 形成的早期阶段，激活的 FGF/MAPK 信号是必需的。此外，与单独的激活素 A 相比，FGF 激活增加了 DE 细胞的数量。这些 DE 细胞可以进一步分化为 PDX1 和 NKX6.1 阳性的胰腺祖细胞。我们得出结论，激活素 A 与 FGF/MAPK 信号的组合在没有血清的情况下有效地诱导 DE 细胞。这些发现提高了我们对内胚层形成的理解，并为生成用于细胞治疗的临床级 hESC 后代迈出了一步。
