Synergistic effects of FGF-2 and Activin A on early neural differentiation of human pluripotent stem cells
Synergistic effects of FGF-2 and Activin A on early neural differentiation of human pluripotent stem cells
复制标题
DOI：
10.1007/s11626-015-9909-8
复制
发表时间：
2015-09-01
影响因子：
2.1
通讯作者：
Furue, Miho K.
中科院分区：
文献类型：
--
作者：
Mimura, Sumiyo;Suga, Mika;Furue, Miho K.
神经分化是人类胚胎干细胞的重要靶标，为细胞治疗、发育生物学和药物研究提供了来源。先前的研究表明，人类胚胎干细胞的神经诱导需要抑制骨形态发生蛋白。相反，成纤维细胞生长因子和Activin/Nodal信号传导的功能存在争议。成纤维细胞生长因子-2 和激活素/Nodal 途径对人胚胎干细胞在多能性和细胞分化的维持方面发挥不同的影响。我们假设不同浓度的成纤维细胞生长因子-2 和激活素 A 的组合可协同地对细胞分化产生不同的影响。为了确定成纤维细胞生长因子-2和激活素A对细胞分化为神经谱系的影响，我们在短期培养的生长因子定义的无血清培养基中检测了用不同浓度的成纤维细胞生长因子-2和/或激活素A处理的人胚胎干细胞中神经分化标记物的表达。在这项研究中，我们提供的证据表明，尽管人胚胎干细胞自主分化为神经细胞谱系，但成纤维细胞生长因子-2 和激活素 A 协同调节人胚胎干细胞分化为神经细胞谱系的起始。
Neural differentiation is an important target of human embryonic stem cells, which provide a source for cell-based therapy, developmental biology, and pharmaceutical research. Previous studies revealed that inhibition of the bone morphogenetic protein is required for neural induction from human embryonic stem cells. On the contrary, the functions of fibroblast growth factors and Activin/Nodal signaling are controversial. Fibroblast growth factor-2 and Activin/Nodal pathways exert divergent influences on human embryonic stem cell concerning the maintenance of both pluripotency and cellular differentiation. We hypothesized that the combination of fibroblast growth factor-2 and Activin A at various concentrations synergistically exerts diverse effects on cell differentiation. To determine the effects of fibroblast growth factor-2 and Activin A on cellular differentiation into neural lineages, we examined the expression of neural differentiation markers in human embryonic stem cells treated with fibroblast growth factor-2 and/or Activin A at various concentrations in a growth factor-defined serum-free medium in short-term culture. In this study, we provide evidence that fibroblast growth factor-2 and Activin A synergistically regulated the initiation of human embryonic stem cell differentiation into neural cell lineages even though human embryonic stem cells autonomously differentiate into neural cell lineages.