The role of FGF-signaling in early neural specification of human embryonic stem cells.
The role of FGF-signaling in early neural specification of human embryonic stem cells.
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DOI：
10.1016/j.ydbio.2010.01.030
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发表时间：
2010-04-15
影响因子：
2.7
通讯作者：
Reubinoff, Benjamin E.
中科院分区：
文献类型：
--
作者：
Cohen, Malkiel A.;Itsykson, Pavel;Reubinoff, Benjamin E.
支配人类神经规范的机制还没有完全确定。在这里，我们使用人胚胎干细胞(HESCs)来研究成纤维细胞生长因子(成纤维细胞生长因子)信号在早期人类神经规范中的作用。分化是通过在化学定义的培养基中培养成簇的hESCs来实现的。我们发现，在hESCs的早期分化过程中，内源性活跃的成纤维细胞生长因子信号诱导了早期的神经规范，而它的阻断则抑制了神经化。成纤维细胞生长因子信号的早期神经化作用并不是通过促进已有神经前体细胞的增殖或阻止其凋亡来实现的。成纤维细胞生长因子信号的神经指导作用发生在最初的成纤维细胞生长因子非依赖性分化成原始外胚层样命运之后。我们进一步表明，成纤维细胞生长因子信号可以通过一种独立于调控骨形态发生蛋白信号的机制来诱导神经化。尽管如此，成纤维细胞生长因子信号对hESC的神经化并不是必需的，在缺少成纤维细胞生长因子和骨形态发生蛋白信号的情况下也可以发生。总而言之，我们的数据表明，人类的神经诱导是由成纤维细胞生长因子信号引导的，尽管hESCs的神经化可以在没有它的情况下发生。
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.
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DOI：
10.1073/pnas.0404700101
发表时间：
2004-08-24
影响因子：
11.1
作者：
Perrier, AL;Tabar, V;Studer, L
通讯作者：
Studer, L
影响因子：
5.2
作者：
Gerrard, L;Rodgers, L;Cui, W
通讯作者：
Cui, W
影响因子：
4.8
作者：
Favata, MF;Horiuchi, KY;Trzaskos, JM
通讯作者：
Trzaskos, JM
影响因子：
46.9
作者：
Chambers, Stuart M.;Fasano, Christopher A.;Papapetrou, Eirini P.;Tomishima, Mark;Sadelain, Michel;Studer, Lorenz
通讯作者：
Studer, Lorenz
影响因子：
0.7
作者：
Eiselleova, Livia;Peterkova, Iveta;Dvorak, Petr
通讯作者：
Dvorak, Petr