Combinatorial analysis of developmental cues efficiently converts human pluripotent stem cells into multiple neuronal subtypes
Combinatorial analysis of developmental cues efficiently converts human pluripotent stem cells into multiple neuronal subtypes
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DOI：
10.1038/nbt.3049
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发表时间：
2015-01-01
影响因子：
46.9
通讯作者：
Nedelec, Stephane
中科院分区：
文献类型：
--
作者：
Maury, Yves;Come, Julien;Nedelec, Stephane
在发育过程中细胞身份的规范取决于细胞暴露于在精确的时间和浓度下传递的外源性线索序列。鉴定控制细胞命运的模式化分子的组合对于有效利用人多能干细胞（hPSC）进行基础和转化研究是必不可少的。在这里，我们描述了一种可扩展的自动化方法，以系统地测试小分子的组合作用，用于hPSC的靶向分化。应用于神经元亚型的产生，该分析揭示了经典Wnt信号传导在指定来自hPSC的运动神经元多样性中的未被认识到的作用，并允许我们定义快速（14天）、有效的程序来产生脊髓和颅运动神经元以及脊髓中间神经元和感觉神经元。我们的系统性方法，以提高hPSC靶向分化应促进疾病建模研究和药物筛选试验。
Specification of cell identity during development depends on exposure of cells to sequences of extrinsic cues delivered at precise times and concentrations. Identification of combinations of patterning molecules that control cell fate is essential for the effective use of human pluripotent stem cells (hPSCs) for basic and translational studies. Here we describe a scalable, automated approach to systematically test the combinatorial actions of small molecules for the targeted differentiation of hPSCs. Applied to the generation of neuronal subtypes, this analysis revealed an unappreciated role for canonical Wnt signaling in specifying motor neuron diversity from hPSCs and allowed us to define rapid (14 days), efficient procedures to generate spinal and cranial motor neurons as well as spinal interneurons and sensory neurons. Our systematic approach to improving hPSC-targeted differentiation should facilitate disease modeling studies and drug screening assays.