Directed differentiation of telencephalic precursors from embryonic stem cells
Directed differentiation of telencephalic precursors from embryonic stem cells
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DOI：
10.1038/nn1402
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发表时间：
2005-03-01
影响因子：
25
通讯作者：
Sasai, Y
中科院分区：
文献类型：
--
作者：
Watanabe, K;Kamiya, D;Sasai, Y
我们展示了利用优化的无血清悬浮培养（SFEB培养）从小鼠胚胎干（ES）细胞中直接分化端脑前体。在SFEB培养的前5天，用Wnt和淋巴结拮抗剂（Dkk1和LeftyA）处理后，ES细胞几乎有选择性地发生神经分化（接近90%）。在有或没有LeftyA的Dkkl存在的情况下，SFEB诱导高效生成表达端脑标志物Bf1的细胞（约35%）。在培养后期，Wnt3a处理增加了苍白端脑细胞群（Pax6（+）细胞产生高达75%的Bf1（+）细胞），而Shh促进基底端脑分化（向Nkx2.1（+）和/或lslet1/2（+）细胞分化），但代价是苍白端脑分化。因此，在缺乏尾状信号的情况下，胚胎干细胞的漂浮聚集体产生幼稚的端脑前体，通过响应细胞外模式信号获得分区域身份。
We demonstrate directed differentiation of telencephalic precursors from mouse embryonic stem (ES) cells using optimized serum-free suspension culture (SFEB culture). Treatment with Wnt and Nodal antagonists (Dkk1 and LeftyA) during the first 5 d of SFEB culture causes nearly selective neural differentiation in ES cells (similar to90%). In the presence of Dkkl, with or without LeftyA, SFEB induces efficient generation (similar to35%) of cells expressing telencephalic marker Bf1. Wnt3a treatment during the late culture period increases the pallial telencephalic population (Pax6(+) cells yield up to 75% of Bf1(+) cells), whereas Shh promotes basal telencephalic differentiation (into Nkx2.1(+) and/or lslet1/2(+) cells) at the cost of pallial telencephalic differentiation. Thus, in the absence of caudalizing signals, floating aggregates of ES cells generate naive telencephalic precursors that acquire subregional identities by responding to extracellular patterning signals.