A High-content screen identifies compounds promoting the neuronal differentiation and the midbrain dopamine neuron specification of human neural progenitor cells
A High-content screen identifies compounds promoting the neuronal differentiation and the midbrain dopamine neuron specification of human neural progenitor cells
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DOI：
10.1038/srep16237
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发表时间：
2015-11-06
影响因子：
4.6
通讯作者：
Wong, Stephen T. C.
中科院分区：
文献类型：
--
作者：
Rhim, Ji Heon;Luo, Xiangjian;Wong, Stephen T. C.
促进干/祖细胞的神经元分化的小分子化合物对于再生医学是至关重要的。我们进行了一个高内容的筛选，以系统地表征已知的生物活性化合物，其对神经元分化和中脑多巴胺（mDA）神经元规格的神经祖细胞（NPC）来自腹侧中脑的人胎脑。在促进化合物中，确定了三种主要的药理学类别，包括他汀类药物、TGF-β RI抑制剂和GSK-3抑制剂。每一类的功能也被证明是不同的，要么促进神经元分化和mDA神经元特化，或选择性后者，或促进前者，但抑制后者。然后，我们进行了初步的调查，可能的机制，并展示了他们的应用程序的NPC来自人类多能干细胞（PSC）。我们的研究揭示了几种小分子化合物用于人NPC定向分化的潜力。筛选结果还提供了对调节人NPC分化的信号网络的深入了解。
Small molecule compounds promoting the neuronal differentiation of stem/progenitor cells are of pivotal importance to regenerative medicine. We carried out a high-content screen to systematically characterize known bioactive compounds, on their effects on the neuronal differentiation and the midbrain dopamine (mDA) neuron specification of neural progenitor cells (NPCs) derived from the ventral mesencephalon of human fetal brain. Among the promoting compounds three major pharmacological classes were identified including the statins, TGF-beta RI inhibitors, and GSK-3 inhibitors. The function of each class was also shown to be distinct, either to promote both the neuronal differentiation and mDA neuron specification, or selectively the latter, or promote the former but suppress the latter. We then carried out initial investigation on the possible mechanisms underlying, and demonstrated their applications on NPCs derived from human pluripotent stem cells (PSCs). Our study revealed the potential of several small molecule compounds for use in the directed differentiation of human NPCs. The screening result also provided insight into the signaling network regulating the differentiation of human NPCs.