Self-Organized Formation of Polarized Cortical Tissues from ESCs and Its Active Manipulation by Extrinsic Signals
Self-Organized Formation of Polarized Cortical Tissues from ESCs and Its Active Manipulation by Extrinsic Signals
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DOI：
10.1016/j.stem.2008.09.002
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发表时间：
2008-11-06
期刊：
影响因子：
23.9
通讯作者：
Sasail, Yoshiki
中科院分区：
文献类型：
--
作者：
Eiraku, Mototsugu;Watanabe, Kiichi;Sasail, Yoshiki
在这里，我们证明了自组织形成的apico-basally极化皮层组织从胚胎干细胞使用一个有效的三维聚集培养（SFEBq文化）。所产生的皮层神经元是功能性的，可移植的，并且能够在体内和体外形成适当的长距离连接。所产生的套膜组织的区域身份可以通过分泌的图案化因子如Fgf、Wnt和BMP选择性地控制（进入嗅球、喙侧和尾侧皮质、血红素和脉络丛）。此外，在体内模仿出生顺序的不同皮层神经元允许选择性生成特定层的特定神经元的定时诱导细胞周期退出。重要的是，由小鼠和人ESC产生的皮质组织形成自组织结构，其包括沿顶-基底方向的沿着四个不同的区（心室、早期和晚期皮质板以及Cajal-Retzius细胞区）。因此，空间和时间方面的早期皮质的重演，并可以在这个ESC文化操纵。
Here, we demonstrate self-organized formation of apico-basally polarized cortical tissues from ESCs using an efficient three-dimensional aggregation culture (SFEBq culture). The generated cortical neurons are functional, transplantable, and capable of forming proper long-range connections in vivo and in vitro. The regional identity of the generated pallial tissues can be selectively controlled (into olfactory bulb, rostral and caudal cortices, hem, and choroid plexus) by secreted patterning factors such as Fgf, Wnt, and BMP. In addition, the in vivo-mimicking birth order of distinct cortical neurons permits the selective generation of particular layer-specific neurons by timed induction of cell-cycle exit. Importantly, cortical tissues generated from mouse and human ESCs form a self-organized structure that includes four distinct zones (ventricular, early and late cortical-plate, and Cajal-Retzius cell zones) along the apico-basal direction. Thus, spatial and temporal aspects of early corticogenesis are recapitulated and can be manipulated in this ESC culture.