Generation of serotonin neurons from human pluripotent stem cells.
Generation of serotonin neurons from human pluripotent stem cells.
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DOI：
10.1038/nbt.3435
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发表时间：
2016-01
影响因子：
46.9
通讯作者：
Zhang SC
中科院分区：
文献类型：
--
作者：
Lu J;Zhong X;Liu H;Hao L;Huang CT;Sherafat MA;Jones J;Ayala M;Li L;Zhang SC
位于后脑中缝核的5-羟色胺神经元在调节脑功能中具有关键作用，并且与各种精神疾病有关。然而，功能性的人类5-羟色胺神经元无法用于体外研究。通过操纵WNT通路，我们证明了人多能干细胞（hPSC）有效分化为类似于中央5-羟色胺神经元的细胞，主要是那些位于喙缝的菱形段2-3中的细胞，这些细胞参与高阶脑功能。5-羟色胺神经元表达一系列对多巴胺能发育至关重要的分子，包括色氨酸羟化酶2，表现出典型的电生理特性，并以活性依赖性方式释放5-羟色胺。当用FDA批准的药物曲马多和草酸依地普仑治疗时，它们以剂量和时间依赖性的方式释放或摄取5-羟色胺，这表明这些细胞可用于评估候选药物。
Serotonin neurons located in the raphe nucleus of the hindbrain have crucial roles in regulating brain functions and have been implicated in various psychiatric disorders. Yet functional human serotonin neurons are not available for in vitro studies. Through manipulation of the WNT pathway, we demonstrate efficient differentiation of human pluripotent stem cells (hPSCs) to cells resembling central serotonin neurons, primarily those located in the rhombomeric segments 2–3 of the rostral raphe, which participate in high-order brain functions. The serotonin neurons express a series of molecules essential for serotonergic development, including tryptophan hydroxylase 2, exhibit typical electrophysiological properties and release serotonin in an activity-dependent manner. When treated with the FDA-approved drugs tramadol and escitalopram oxalate, they release or uptake serotonin in a dose- and time-dependent manner, suggesting the utility of these cells for the evaluation of drug candidates.