Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Development. 2014 Feb;141(3):491-501. doi: 10.1242/dev.097410.
All muscle movements, including breathing, walking, and fine motor skills rely on the function of the spinal motor neuron to transmit signals from the brain to individual muscle groups. Loss of spinal motor neuron function underlies several neurological disorders for which treatment has been hampered by the inability to obtain sufficient quantities of primary motor neurons to perform mechanistic studies or drug screens. Progress towards overcoming this challenge has been achieved through the synthesis of developmental biology paradigms and advances in stem cell and reprogramming technology, which allow the production of motor neurons in vitro. In this Primer, we discuss how the logic of spinal motor neuron development has been applied to allow generation of motor neurons either from pluripotent stem cells by directed differentiation and transcriptional programming, or from somatic cells by direct lineage conversion. Finally, we discuss methods to evaluate the molecular and functional properties of motor neurons generated through each of these techniques.
所有的肌肉运动，包括呼吸、行走和精细运动技能，都依赖于脊髓运动神经元的功能，将信号从大脑传递到各个肌肉群。几种神经紊乱疾病的基础是脊髓运动神经元功能的丧失，而治疗这些疾病的障碍是无法获得足够数量的原始运动神经元来进行机制研究或药物筛选。通过综合发展生物学范例以及干细胞和重编程技术的进步，已经在克服这一挑战方面取得了进展，这些技术允许在体外产生运动神经元。在这篇专题论文中，我们讨论了如何应用脊髓运动神经元发育的逻辑，从多能干细胞通过定向分化和转录编程产生运动神经元，或者从体细胞通过直接谱系转换产生运动神经元。最后，我们讨论了通过这些技术中的每一种方法来评估运动神经元的分子和功能特性的方法。
