Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors.
Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors.
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DOI：
10.1038/nbt.2249
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发表时间：
2012-07-01
影响因子：
46.9
通讯作者：
中科院分区：
文献类型：
--
作者：
在鉴定指导人多能干细胞（hPSC）分化为包括神经元在内的特化细胞类型的信号传导途径方面已经取得了相当大的进展。然而，基于外源因子的hPSC分化是一个缓慢的、逐步的过程，模拟了正常人类发育的延长时间。使用小分子筛选，我们鉴定了足以在分化的10天内以>75%的效率产生hPSC衍生的神经元的五种小分子途径抑制剂的组合。所得到的神经元表达人类伤害感受器的典型标志物和功能特性，包括TTX抗性、SCN 10A依赖性钠电流和对伤害性刺激（包括ATP和辣椒素）的响应。神经元命运的获取比体内发育快三倍，这表明使用小分子途径抑制剂可以发展成为一种加速体外发育时机的通用策略。伤害感受器的快速高效衍生为人类疼痛研究提供了前所未有的医学相关细胞类型。
There has been considerable progress in identifying signaling pathways directing the differentiation of human pluripotent stem cells (hPSCs) into specialized cell types including neurons. However, extrinsic factor-based differentiation of hPSCs is a slow, step-wise process mimicking the protracted timing of normal human development. Using a small molecule screen we identified a combination of five small molecule pathway inhibitors sufficient to yield hPSC-derived neurons at >75% efficiency within 10 days of differentiation. The resulting neurons express canonical markers and functional properties of human nociceptors including TTX-resistant, SCN10A-dependent sodium currents and response to nociceptive stimuli including ATP and capsaicin. Neuronal fate acquisition occurs three-fold faster than during in vivo development suggesting that use of small molecule pathway inhibitors could develop into a general strategy for accelerating developmental timing in vitro. The quick and high efficiency derivation of nociceptors offers unprecedented access to this medically relevant cell type for studies of human pain.
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影响因子：
25
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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影响因子：
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作者：
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通讯作者：
Studer L
DOI：
10.1073/pnas.90.22.10841
发表时间：
1993-11-15
影响因子：
11.1
作者：
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通讯作者：
ROSENFELD, MG