SOX21 Ensures Rostral Forebrain Identity by Suppression of WNT8B during Neural Regionalization of Human Embryonic Stem Cells
SOX21 Ensures Rostral Forebrain Identity by Suppression of WNT8B during Neural Regionalization of Human Embryonic Stem Cells
复制标题
SOX21 在人胚胎干细胞的神经区域化过程中通过抑制 WNT8B 确保前脑的同一性
DOI：
10.1016/j.stemcr.2019.10.013
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发表时间：
2019-12-10
影响因子：
5.9
通讯作者：
Jin, Ying
中科院分区：
文献类型：
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作者：
Fang, Zhuoqing;Liu, Xinyuan;Jin, Ying
从人胚胎干细胞（hESCs）中产生脑区域特异性祖细胞是其应用的关键。然而，人类神经区域化的转录调控知之甚少。在这里，我们应用了一个rostrocaudal图案系统从人胚胎干细胞解剖全球转录网络控制早期神经区域化。我们发现，SOX 21是所需的喙前脑命运规范。SOX 21基因敲除导致Wnt信号的激活，导致吻侧前脑神经祖细胞区域身份的尾化。此外，我们将WNT 8B确定为SOX 21的直接靶标。在SOX 21敲除的神经祖细胞中，WNT 8B的缺失或Wnt信号传导的抑制恢复了吻侧前脑的特性。此外，SOX 21与β-连环蛋白相互作用，干扰TCF 4/β-连环蛋白复合物与WNT 8B增强子的结合。总的来说，这些结果揭示了SOX 21的未知作用，并揭示了转录因子如何通过与Wnt信号传导的关键成分的串扰来调节早期神经区域化。
The generation of brain region-specific progenitors from human embryonic stem cells (hESCs) is critical for their application. However, transcriptional regulation of neural regionalization in humans is poorly understood. Here, we applied a rostrocaudal patterning system from hESCs to dissect global transcriptional networks controlling early neural regionalization. We found that SOX21 is required for rostral forebrain fate specification. SOX21 knockout led to activation of Wnt signaling, resulting in caudalization of regional identity of rostral forebrain neural progenitor cells. Moreover, we identified WNT8B as a SOX21 direct target. Deletion of WNT8B or inhibition of Wnt signaling in SOX21 knockout neural progenitor cells restored rostral forebrain identity. Furthermore, SOX21 interacted with beta-catenin, interfering with the binding of TCF4/beta-catenin complex to the WNT8B enhancer. Collectively, these results unveil the unknown role of SOX21 and shed light on how a transcriptional factor modulates early neural regionalization through crosstalk with a key component of Wnt signaling.