Functional diversity of ESC-derived motor neuron subtypes revealed through intraspinal transplantation.

Functional diversity of ESC-derived motor neuron subtypes revealed through intraspinal transplantation.
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DOI:
10.1016/j.stem.2010.07.013
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发表时间:
2010-09-03
期刊:
影响因子:
23.9
通讯作者:
Wichterle H
Wichterle H
中科院分区:
医学1区
文献类型:
--
作者:
Peljto M;Dasen JS;Mazzoni EO;Jessell TM;Wichterle H

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培养的ES细胞可以形成不同类型的神经元,但这些神经元是否可以获得体内神经元典型的特化亚型特征仍不清楚。我们在这里表明,小鼠ES细胞可以直接形成高度特异性的运动神经元亚型在没有添加的因素,通过分化程序,依赖于内源性Wnt,FGF,和Hh -模仿运动神经元亚型分化的正常程序。表征运动神经元亚型的分子标记物预测这些神经元在体内的功能特性:等时移植到鸡脊髓中的ES运动神经元在适当的柱状域中定居,并选择轴突轨迹与其在体内产生的对应物的保真度相匹配。因此,ES运动神经元可以以预测的方式编程,以获得表征体内存在的数十种特化运动神经元亚型之一的分子和功能特性。
Cultured ES cells can form different classes of neurons, but whether these neurons can acquire specialized subtype features typical of neurons in vivo remains unclear. We show here that mouse ES cells can be directed to form highly specific motor neuron subtypes in the absence of added factors, through a differentiation program that relies on endogenous Wnts, FGFs, and Hh – mimicking the normal program of motor neuron subtype differentiation. Molecular markers that characterize motor neuron subtypes anticipate the functional properties of these neurons in vivo: ES motor neurons grafted isochronically into chick spinal cord settle in appropriate columnar domains and select axonal trajectories with a fidelity that matches that of their in vivo generated counterparts. ES motor neurons can therefore be programmed in a predictive manner to acquire molecular and functional properties that characterize one of the many dozens of specialized motor neuron subtypes that exist in vivo.
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