Primitive neural stem cells from the mammalian epiblast differentiate to definitive neural stem cells under the control of Notch signaling
Primitive neural stem cells from the mammalian epiblast differentiate to definitive neural stem cells under the control of Notch signaling
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DOI：
10.1101/gad.1208404
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发表时间：
2004-08-01
影响因子：
10.5
通讯作者：
van der Kooy, D
中科院分区：
文献类型：
--
作者：
Hitoshi, S;Seaberg, RM;van der Kooy, D
基本成纤维细胞生长因子（FGF2）应答的终级神经干细胞首先出现在胚胎期8.5天（E8.5）的小鼠胚胎中，但在更早的胚胎中没有出现，尽管神经组织在E7.5就存在了。在这里，我们证明白血病抑制因子依赖（但不依赖于fgf2）的球形细胞存在于早期（E5.5-E7.5）小鼠胚胎中。由此产生的克隆球细胞具有自我更新能力和神经多能性，这是神经干细胞的主要特征。然而，它们也保留了一些非神经性质，这表明它们是体内细胞的等效原始神经干细胞，从胚胎干细胞在体外形成。体内原始神经干细胞的生成独立于Notch信号，但Notch通路的激活对于从原始神经干细胞向完全定形神经干细胞性质的转变以及维持定形神经干细胞状态至关重要。
Basic fibroblast growth factor (FGF2)-responsive definitive neural stem cells first appear in embryonic day 8.5 (E8.5) mouse embryos, but not in earlier embryos, although neural tissue exists at E7.5. Here, we demonstrate that leukemia inhibitory factor-dependent (but not FGF2-dependent) sphere-forming cells are present in the earlier (E5.5-E7.5) mouse embryo. The resultant clonal sphere cells possess self-renewal capacity and neural multipotentiality, cardinal features of the neural stem cell. However, they also retain some nonneural properties, suggesting that they are the in vivo cells' equivalent of the primitive neural stem cells that form in vitro from embryonic stem cells. The generation of the in vivo primitive neural stem cell was independent of Notch signaling, but the activation of the Notch pathway was important for the transition from the primitive to full definitive neural stem cell properties and for the maintenance of the definitive neural stem cell state.