The Hadassah Human Embryonic Stem Cell Research Center, The Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Dev Biol. 2010 Apr 15;340(2):450-8. doi: 10.1016/j.ydbio.2010.01.030. Epub 2010 Feb 10.
The mechanisms that govern human neural specification are not completely characterized. Here we used human embryonic stem cells (hESCs) to study the role of fibroblast growth factor (FGF)-signaling in early human neural specification. Differentiation was obtained by culturing clusters of hESCs in chemically-defined medium. We show that FGF-signaling, which is endogenously active during early differentiation of hESCs, induces early neural specification, while its blockage inhibits neuralization. The early neuralization effect of FGF-signaling is not mediated by promoting the proliferation of existing neural precursors (NPs) or prevention of their apoptosis. The neural instructive effect of FGF-signaling occurs after an initial FGF-independent differentiation into primitive ectoderm-like fate. We further show that FGF-signaling can induce neuralization by a mechanism which is independent of modulating bone morphogenic protein (BMP)-signaling. Still, FGF-signaling is not essential for hESC neuralization which can occur in the absence of FGF and BMP-signaling. Collectively, our data suggest that human neural induction is instructed by FGF-signaling, though neuralization of hESCs can occur in its absence.
调控人类神经特化的机制尚未完全阐明。在这里，我们利用人类胚胎干细胞（hESC）来研究成纤维细胞生长因子（FGF）信号在早期人类神经特化中的作用。通过在化学定义的培养基中培养 hESC 簇来获得分化。我们表明，在 hESC 早期分化过程中内源性活跃的 FGF 信号诱导早期神经特化，而其阻断则抑制神经化。FGF 信号的早期神经化作用不是通过促进现有神经前体（NPs）的增殖或防止其凋亡来介导的。FGF 信号的神经指令作用发生在初始 FGF 独立分化为原始外胚层样命运之后。我们进一步表明，FGF 信号可以通过一种独立于调节骨形态发生蛋白（BMP）信号的机制诱导神经化。尽管如此，FGF 信号对于 hESC 的神经化并非必需，因为在没有 FGF 和 BMP 信号的情况下也可以发生神经化。总的来说，我们的数据表明，尽管在没有 FGF 和 BMP 信号的情况下也可以发生神经化，但人类神经诱导受到 FGF 信号的指示。
